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carbamoyl phosphate + L-asparagine
phosphate + N-carbamoyl-L-asparagine
-
the enzyme catalyzes the carbamoylation of L-Asn with a Km of 122 mM and a maximal velocity 10fold lower than observed with the natural substrate, L-Asp. As opposed to L-Asp, no cooperativity is observed with respect to L-Asn
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
L-aspartate + carbamoyl phosphate
phosphate + N-carbamoyl-L-aspartate
additional information
?
-
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
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-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
the enzyme catalyzes the first committed step in pyrimidine biosynthesis
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
substrate binding causes significant conformational changes
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
Arg229, which interacts with the beta-carboxylate of L-Asp, plays a critical role in the orientation of L-Asp in the active site and demonstrates the requirement of the beta-carboxylate of L-Asp in the mechanism of domain closure and the allosteric transition in Escherichia coli ATCase
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
upon substrate binding, allosteric Escherichia coli aspartate transcarbamoylase adopts alternate quaternary structures, stabilized by a set of interdomain and intersubunit interactions, which are readily differentiated by their solution x-ray scattering curves. The cooperative binding of aspartate in aspartate transcarbamoylase appears to result from the combination of the preexisting quaternary structure equilibrium with local changes induced by binding of carbamoyl phosphate
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-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
the enzyme catalyzes the first step in the pyrimidine biosynthetic pathway
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
the enzyme catalyzes the first step in the pyrimidine biosynthetic pathway
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
Pigeon
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
Pseudomonas vulgaris
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
there is no preferential partitioning of carbamoyl phosphate between the arginine and pyrimidine biosynthetic pathways. Channeling must occur during the dynamic association of coupled enzymes pairs. The interaction of carbamoyl-phosphate synthetase/aspartate transcarbamoylase is demonstrated by the unexpectedly weak inhibition of the coupled reaction by the bisubstrate analog, N-(phosphonacetyl)-L-aspartate. In the coupled reaction, the effective concentration of carbamoyl phosphate in the vicinity of the aspartate transcarbamoylase active site is 96fold higher than the concentration in the bulk phase. Channeling probably plays an essential role in protecting this very unstable intermediate of metabolic pathways performing at extreme temperatures
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-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
specific for L-aspartate
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
second enzyme of pyrimidine synthesis
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
catalyzes the formation of carbamoyl-L-aspartate, the first compound unique to the biosynthetic pathway for pyrimidine nucleotides
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
catalyzes the formation of carbamoyl-L-aspartate, the first compound unique to the biosynthetic pathway for pyrimidine nucleotides
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
Pigeon
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
Pseudomonas vulgaris
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
L-aspartate + carbamoyl phosphate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
L-aspartate + carbamoyl phosphate
phosphate + N-carbamoyl-L-aspartate
carbamoyl phosphate binding structure, in silico docking and electrostatic calculations, overview
-
-
?
L-aspartate + carbamoyl phosphate
phosphate + N-carbamoyl-L-aspartate
-
-
-
-
?
L-aspartate + carbamoyl phosphate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
L-aspartate + carbamoyl phosphate
phosphate + N-carbamoyl-L-aspartate
-
-
i.e. ureidosuccinic acid
-
?
L-aspartate + carbamoyl phosphate
phosphate + N-carbamoyl-L-aspartate
-
ATCase displays ordered substrate binding and product release, remaining in the R state until substrates are exhausted. Wild-type ATCase is in a T-state structure with bound product phosphate
-
-
?
L-aspartate + carbamoyl phosphate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
additional information
?
-
-
CAD is a rate-limiting enzyme required for the formation of UDP sugar, upstream of two different metabolic pathways; the de novo biosynthesis of pyrimidine and pyrimide-based nucleotides, and the formation of UDP sugar intermediates, required for UDP-dependent glycosylation events
-
-
?
additional information
?
-
-
the allosteric enzyme shows homotropic cooperative interactions between the catalytic sites for the binding of aspartate due to a quarternary structure transition between high aspartate affinity T state and R state
-
-
?
additional information
?
-
-
concerted transition between structural and functional states of either low affinity, low activity or high affinity, high activity for aspartate. Addition of ATP along with the substrates increases the rate of the transition from the T to the R state and also decreases the duration of the R-state steady-state phase. Addition of CTP or the combination of CTP/UTP to the substrates significantly decreases the rate of the T-R transition and causes a shift in the enzyme population towards the T state even at saturating substrate concentrations
-
-
?
additional information
?
-
conformational changes due to nucleotide binding, overview
-
-
?
additional information
?
-
-
conformational changes due to nucleotide binding, overview
-
-
?
additional information
?
-
-
in the structure of the enzyme trapped in the R state with specific disulfide bonds, two phosphate molecules are bound per active site. The position of the first phosphate corresponds to the position of the phosphate of carbamoyl phosphate and the position of the phosphonate of inhibitor N-phosphonacetyl-L-aspartate. However, the second, more weakly bound phosphate is bound in a positively charged pocket that is more accessible to the surface than the other phosphate. The second phosphate appears to be on the path that phosphate would have to take to exit the active site
-
-
?
additional information
?
-
-
link between enzyme activity and gametogenesis
-
-
?
additional information
?
-
-
ACT-DHOD gene is transcribed to ACT-DHOD mRNA, translated to the single protein, ACT-DHOD, and finally converted to mature independent DHOD and ACT
-
-
?
additional information
?
-
-
direct intermolecular interactions between the enzymes catalyzing the first three reaction steps of the de novo pyrimidine biosynthetic pathway, carbamoylphosphate synthetase II (CPSII), aspartate transcarbamoylase (ATC), and dihydroorotase (DHO), of the parasitic protist Trypanosoma cruzi, interaction analysis, overview
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
L-aspartate + carbamoyl phosphate
phosphate + N-carbamoyl-L-aspartate
additional information
?
-
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
the enzyme catalyzes the first committed step in pyrimidine biosynthesis
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
the enzyme catalyzes the first step in the pyrimidine biosynthetic pathway
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
the enzyme catalyzes the first step in the pyrimidine biosynthetic pathway
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
there is no preferential partitioning of carbamoyl phosphate between the arginine and pyrimidine biosynthetic pathways. Channeling must occur during the dynamic association of coupled enzymes pairs. The interaction of carbamoyl-phosphate synthetase/aspartate transcarbamoylase is demonstrated by the unexpectedly weak inhibition of the coupled reaction by the bisubstrate analog, N-(phosphonacetyl)-L-aspartate. In the coupled reaction, the effective concentration of carbamoyl phosphate in the vicinity of the aspartate transcarbamoylase active site is 96fold higher than the concentration in the bulk phase. Channeling probably plays an essential role in protecting this very unstable intermediate of metabolic pathways performing at extreme temperatures
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
second enzyme of pyrimidine synthesis
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
catalyzes the formation of carbamoyl-L-aspartate, the first compound unique to the biosynthetic pathway for pyrimidine nucleotides
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
catalyzes the formation of carbamoyl-L-aspartate, the first compound unique to the biosynthetic pathway for pyrimidine nucleotides
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
Pigeon
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
Pseudomonas vulgaris
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
L-aspartate + carbamoyl phosphate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
L-aspartate + carbamoyl phosphate
phosphate + N-carbamoyl-L-aspartate
-
-
-
-
?
L-aspartate + carbamoyl phosphate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
L-aspartate + carbamoyl phosphate
phosphate + N-carbamoyl-L-aspartate
-
-
i.e. ureidosuccinic acid
-
?
L-aspartate + carbamoyl phosphate
phosphate + N-carbamoyl-L-aspartate
-
-
-
?
additional information
?
-
-
CAD is a rate-limiting enzyme required for the formation of UDP sugar, upstream of two different metabolic pathways; the de novo biosynthesis of pyrimidine and pyrimide-based nucleotides, and the formation of UDP sugar intermediates, required for UDP-dependent glycosylation events
-
-
?
additional information
?
-
-
link between enzyme activity and gametogenesis
-
-
?
additional information
?
-
-
ACT-DHOD gene is transcribed to ACT-DHOD mRNA, translated to the single protein, ACT-DHOD, and finally converted to mature independent DHOD and ACT
-
-
?
additional information
?
-
-
direct intermolecular interactions between the enzymes catalyzing the first three reaction steps of the de novo pyrimidine biosynthetic pathway, carbamoylphosphate synthetase II (CPSII), aspartate transcarbamoylase (ATC), and dihydroorotase (DHO), of the parasitic protist Trypanosoma cruzi, interaction analysis, overview
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
(2S)-2-(([hydroxy(hydroxymethyl)phosphoryl]acetyl)amino)butanedioic acid
-
competitive
(2S)-2-(([hydroxy(oxido)-lambda5-phosphanyl]acetyl)amino)butanedioic acid
-
competitive
1,4,6,7-tetrabromo-2,3-naphthalenediol
-
2,2-dimethylsuccinate
-
-
2,3-naphthalenediol
non-competitive inhibitor
2-(4-hydroxy-2,4-dioxo-4lamdba5-[1,4]azaphosphinan-1-yl)-succinic acid
-
competitive
2-methylquinazolin-4(3H)-one
-
-
2-phenyl-1,3-4(H)benzothiazin-4-thione
-
noncompetitive inhibitor towards both aspartate and carbamoyl phosphate
3-amino-6,8-dibromo-2-methyl-4(3H)-quinazolinone
-
-
3-amino-6,8-dibromo-2-phenyl-4-(3H)-quinazolinone
-
noncompetitive
4,5-dicarboxy-2-ketopentylphosphonate
-
-
4-(3-methyl-2,4,6-trioxo-2,3,4,5,6,11-hexahydro-1H-indeno[2',1':5,6]pyrido[2,3-d]pyrimidin-5-yl)phenyl 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propanoate
5'-UMP
-
2'-UMP and 3'-UMP have no effect
5-([6-[(2E)-2-([2-[(2,4-dichlorophenyl)methoxy]phenyl]methylidene)hydrazinyl][1,2,5]oxadiazolo[3,4-b]pyrazin-5-yl]amino)-1,3-dihydro-2H-benzimidazol-2-one
6,7-dibromo-2,3-naphthalenediol
-
Carbonyldiphosphonate
-
-
dichlormethylenediphosphonate
-
-
Diphosphate analogues
-
-
-
Guanidine-HCl
-
800 mM, almost complete inhibition
HgCl2
-
0.001 mM, 50% inhibition
Mersalyl
-
0.01 mM, 50% inhibition
Methylenediphosphonate
-
-
N-(2-hydroxy-acetyl)-L-aspartic acid-phosphate
-
competitive
N-(phosphonacetyl)-L-aspartate
N-(Phosphonoacetyl)-L-aspartate
N-(phosphonoacetyl)-L-aspartic acid
-
-
N-Diphosphoryl-L-aspartate
-
-
N-methyl phosphonoacetamide
-
-
N-phosphonacetyl-L-asparagine
-
potent inhibitor of ATCase
N-phosphonacetyl-L-aspartate
N-phosphonoacetyl-L-aspartate
N-phosphoryl-L-aspartate
-
-
N-pyrophosphoryl-L-aspartate
-
-
O-phosphonoacetyl-oxosuccinate
-
-
p-mercuribenzoate
-
0.01 mM, 50% inhibition
Phosphonoacetic acid
-
1 mM, 50% inhibition
S-diphosphoryl-mercaptosuccinate
-
-
S-phosphonoacetyl-mercaptosuccinate
-
-
Urea
-
2.5 M, almost complete inhibition
4-(3-methyl-2,4,6-trioxo-2,3,4,5,6,11-hexahydro-1H-indeno[2',1':5,6]pyrido[2,3-d]pyrimidin-5-yl)phenyl 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propanoate
-
4-(3-methyl-2,4,6-trioxo-2,3,4,5,6,11-hexahydro-1H-indeno[2',1':5,6]pyrido[2,3-d]pyrimidin-5-yl)phenyl 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propanoate
-
-
5-([6-[(2E)-2-([2-[(2,4-dichlorophenyl)methoxy]phenyl]methylidene)hydrazinyl][1,2,5]oxadiazolo[3,4-b]pyrazin-5-yl]amino)-1,3-dihydro-2H-benzimidazol-2-one
-
5-([6-[(2E)-2-([2-[(2,4-dichlorophenyl)methoxy]phenyl]methylidene)hydrazinyl][1,2,5]oxadiazolo[3,4-b]pyrazin-5-yl]amino)-1,3-dihydro-2H-benzimidazol-2-one
-
-
acetyl phosphate
-
3 mM, 50% inhibition
ADP
-
5 mM, 19% residual activity
ADP
-
5 mM, 8% residual activity
aspartate
-
-
aspartate
-
at high concentrations
ATP
-
dual regulatory pattern, activating the enzyme at low concentrations and inhibiting it in the mM range
ATP
-
excess MgCl2 abolishes inhibition
ATP
-
5 mM, 8% residual activity
ATP
inhibitory effect on the catalytic subunits encoded by the sole pyrB gene. The complete ATCase purified from recombinant Escherichia coli is strongly activated
ATP
-
1 mM, 40% inhibition
carbamoyl aspartate
-
-
carbamoyl aspartate
-
noncompetitive vs. carbamoyl phosphate and aspartate
CDP
-
10 mM, 61% inhibition
CDP
-
5 mM, 23% residual activity
CTP
-
800-1000 mM urea lower or eliminate CTP inhibition
CTP
-
synergistic inhibition by CTP and UTP
CTP
-
competitive vs. carbamoyl phosphate
CTP
-
synergistic inhibition by CTP and UTP
CTP
-
CTP inhibits ATCase activity. Experimentally driven, statistical modeling approach (high-dimensional model representation, RS-HDMR) to investigate regulation of ATCase in response to varying concentrations of its nucleotide regulators ATP, CTP, GTP, and UTP (at fixed substrate concentrations)
CTP
-
addition of CTP or the combination of CTP/UTP to the substrates significantly decreases the rate of the low activity-high activity T-R transition and causes a shift in the enzymepopulation towards the T state even at saturating substrate concentrations
CTP
-
ATCase is feedback inhibited by CTP and synergistically by the combination of CTP plus UTP
CTP
aspartate transcarbamoylase is feedback inhibited by CTP in the presence of CTP. CTP and UTP do not bind competitively, CTP binding structure, overview
CTP
demetaled CTP, synergistic inhibition with UTP, while UTP alone has little or no influence on the enzyme activity, mechanism, overview. Binding of UTP can enhance the binding of CTP and presence of a metal ion such as Mg2+ is required for synergistic inhibition. Structure of the ATCase-CTP-UTP-Mg2+ complex
CTP
-
10 mM, 79% inhibition
CTP
-
5 mM, 4% residual activity
CTP
-
5 mM, 37% residual activity
CTP
-
allosteric inhibitor
CTP
inhibitory effect on the catalytic subunits encoded by the sole pyrB gene. The complete ATCase purified from recombinant Escherichia coli is strongly activated
CTP
2 mM, about 90% inhibition
diphosphate
-
-
diphosphate
-
5 mM, 6% residual activity
diphosphate
-
5 mM, 10% residual activity
GDP
-
5 mM, 39% residual activity
GDP
-
5 mM, 38% residual activity
GTP
-
-
GTP
-
GTP inhibits ATCase activity. Experimentally driven, statistical modeling approach (high-dimensional model representation, RS-HDMR) to investigate regulation of ATCase in response to varying concentrations of its nucleotide regulators ATP, CTP, GTP, and UTP (at fixed substrate concentrations)
GTP
-
5 mM, 11% residual activity
GTP
inhibitory effect on the catalytic subunits encoded by the sole pyrB gene. The complete ATCase purified from recombinant Escherichia coli is strongly activated
GTP
-
1 mM, 20% inhibition
iodoacetate
-
-
Maleate
-
-
Maleate
-
15 mM, 50% inhibition
N-(phosphonacetyl)-L-aspartate
-
treatment of seedling with 1 mM, results in delayed germination, inhibition of cotyledon expansion, leaf development and root growth. 2fold increase in enzyme activity and protein level
N-(phosphonacetyl)-L-aspartate
-
-
N-(phosphonacetyl)-L-aspartate
-
-
N-(phosphonacetyl)-L-aspartate
there is no preferential partitioning of carbamoyl phosphate between the arginine and pyrimidine biosynthetic pathways. Channeling must occur during the dynamic association of coupled enzymes pairs. The interaction of carbamoyl-phosphate synthetase/aspartate transcarbamoylase is demonstrated by the unexpectedly weak inhibition of the coupled reaction by the bisubstrate analog, N-(phosphonacetyl)-L-aspartate
N-(Phosphonoacetyl)-L-aspartate
-
-
N-(Phosphonoacetyl)-L-aspartate
-
-
N-(Phosphonoacetyl)-L-aspartate
-
0.0001 mM, 50% inhibition
N-(Phosphonoacetyl)-L-aspartate
-
-
N-(Phosphonoacetyl)-L-aspartate
-
0.011 mM, 50% inhibition, low concentrations activate
N-(Phosphonoacetyl)-L-aspartate
0.002 mM, 50% inhibition of catalytic subunit
N-(Phosphonoacetyl)-L-aspartate
-
-
N-(Phosphonoacetyl)-L-aspartate
-
competitive vs. carbamoyl phosphate, noncompetitive vs. aspartate
N-phosphonacetyl-L-aspartate
-
binding of the bisubstrate analogue N-phosphonacetyl-L-aspartate to the aspartate transcarbamoylase subunit inhibits the activity of the distal dihydroorotase subunit
N-phosphonacetyl-L-aspartate
a bisubstrate/transition state analogue, binding structure, in silico docking and electrostatic calculations, overview
N-phosphonacetyl-L-aspartate
-
-
N-phosphonacetyl-L-aspartate
-
PALA, a bisubstrate transition state analogue, and shows also ability of PALA to enhance the activity of ATCase at low concentrations of aspartate, in the presence of a saturating concentration of carbamoyl phosphat. Interactions between the side chain of Gln137 and the backbone carbonyl oxygen of Pro266 to the amino group on the tetrahedral carbon and the side chain of Arg54 with the ester oxygen between the phosphorus and the tetrahedral carbone
N-phosphonacetyl-L-aspartate
-
i.e. PALA, a bisubstrate analogue, the binding of PALA is able to stabilize the enzyme in the high-activity, high-affinity R state because its structure mimics the reaction's transition state structure. The concerted transition to the R state allows a majority of active sites free to react with substrates and release products while a minority of active sites bound with PALA are inactive but stabilize the enzyme in the R state. Therefore, at low concentrations of PALA the activity increases; however, as the concentration of PALA is increased more and more of the active sites are filled by the non-hydrolyzable bisubstrate analog and the activity drops. At high concentrations of Asp and a saturating concentration of carbamoyl phosphate, no PALA activation is observed. In the absence of allosteric effectors the average KD of PALA is 110 nM, decreasing to 65 nM in the presence of ATP and increasing to 266 nM in the presence of CTP
N-phosphonacetyl-L-aspartate
-
-
N-phosphonacetyl-L-aspartate
-
N-phosphonoacetyl-L-aspartate
-
competitive
N-phosphonoacetyl-L-aspartate
-
after addition of N-phosphonacetyl-L-aspartate to the enzyme, the transition rate is more than 1 order of magnitude slower than with the natural substrates
N-phosphonoacetyl-L-aspartate
binding structure, overview
nucleotides
-
-
-
p-chloromercuribenzoate
-
-
p-chloromercuribenzoate
-
6 mM, almost complete inhibition
p-hydroxymercuribenzoate
-
-
p-hydroxymercuribenzoate
-
strong inhibition
Phenobarbital
-
-
phosphate
-
-
phosphate
-
competitive vs. carbamoyl phosphate, noncompetitive vs. aspartate
succinate
-
-
succinate
-
10 mM, 50% inhibition
succinate
-
activator at low concentrations of both succinate and aspartate, inhibitor at high succinate concentrations and at high aspartate concentrations
Thiobarbituric acid
-
most potent inhibitor
Thiobarbituric acid
-
most potent inhibitor
thymidine
-
-
UDP
-
5 mM, 11% residual activity
UDP
-
5 mM, 7% residual activity
UDP
-
1 mM, 45% inhibition
UMP
-
-
UMP
-
5 mM, 6% residual activity
UMP
-
5 mM, 21% residual activity
UMP
-
0.1 mM, 25% inhibition, inhibition increases to 80% and 90% in the presence of 0.2 mM and 0.6 mM deoxycholate respectively
UMP
-
fatty acids with chains of C8 or longer, dodecylsulfate and decylsulfonate potentiate inhibition
UMP
-
0.8 mM, 85% inhibition
UMP
-
1 mM, 75% inhibition
UTP
-
weak inhibition
UTP
-
synergistic inhibition by CTP and UTP, no inhibition unless CTP is present
UTP
-
UTP inhibits ATCase activity. Experimentally driven, statistical modeling approach (high-dimensional model representation, RS-HDMR) to investigate regulation of ATCase in response to varying concentrations of its nucleotide regulators ATP, CTP, GTP, and UTP (at fixed substrate concentrations)
UTP
-
addition of CTP or the combination of CTP/UTP to the substrates significantly decreases the rate of the low activity-high activity T-R transition and causes a shift in the enzymepopulation towards the T state even at saturating substrate concentrations
UTP
aspartate transcarbamoylase is feedback inhibited by UTP in the presence of CTP. UTP binds to a unique site on each regulatory chain of the enzyme that is near but not overlapping with the known CTP site. CTP and UTP do not bind competitively, UTP binds to the r6 regulatory chain of ATCase, UTP binding structure, overview
UTP
inhibition with CTP, while UTP alone has little or no influence on the enzyme activity, mechanism, overview. UTP, in the presence of dCTP or CTP, binds at a site on a regulatory side chain that does not overlap the CTP/dCTP site, and the triphosphates of the two nucleotides are parallel to each other with a metal ion, in this case Mg2+, coordinated between the beta- and gamma-phosphates of the two nucleotides. UTP binds more tightly in the presence of CTP. Structure of the ATCase-CTP-UTP-Mg2+ complex
UTP
UTP is able to synergistically inhibit ATCase in the presence of CTP, but UTP alone has little or no influence on activity
UTP
-
allosteric inhibitor
UTP
inhibitory effect on the catalytic subunits encoded by the sole pyrB gene. The complete ATCase purified from recombinant Escherichia coli is strongly activated
UTP
2 mM, about 90% inhibition
UTP
-
1 mM, 40% inhibition
additional information
conformational changes due to nucleotide binding, overview
-
additional information
-
conformational changes due to nucleotide binding, overview
-
additional information
CTP and dCTP bind in a very similar fashion, UTP, in the presence of dCTP or CTP, binds at a site that does not overlap the CTP/dCTP site, and the triphosphates of the two nucleotides are parallel to each other with a metal ion, in this case Mg2+, coordinated between the beta- and gamma-phosphates of the two nucleotides, synergistic Inhibition of ATCase by CTP and UTP is metal-dependent, Mg2+ and Mn2+ act best, binding structures, overview
-
additional information
-
CTP and dCTP bind in a very similar fashion, UTP, in the presence of dCTP or CTP, binds at a site that does not overlap the CTP/dCTP site, and the triphosphates of the two nucleotides are parallel to each other with a metal ion, in this case Mg2+, coordinated between the beta- and gamma-phosphates of the two nucleotides, synergistic Inhibition of ATCase by CTP and UTP is metal-dependent, Mg2+ and Mn2+ act best, binding structures, overview
-
additional information
not inhibited by fluorouracil
-
additional information
-
not inhibited by fluorouracil
-
additional information
-
not inhibited by CTP
-
additional information
-
50% inhibition at 80 MPa; not inhibited by phosphonoacetate, diphosphate or phosphate
-
additional information
-
kinetic analysis of properties of allosteric effectors alone and in combination with each other
-
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Anemia, Hypochromic
Mode of Action of the Toxin from Pseudomonas phaseolicola: I. Toxin Specificity, Chlorosis, and Ornithine Accumulation.
Anemia, Hypoplastic, Congenital
Elevation of pyrimidine enzyme activities in the RBC of patients with congenital hypoplastic anaemia and their parents.
Brain Neoplasms
Pyrimidine pathways enzymes in human tumors of brain and associated tissues: potentialities for the therapeutic use of N-(phosphonacetyl-L-aspartate and 1-beta-D-arabinofuranosylcytosine.
Carcinoma
The effects of pH and inhibitors upon the catalytic activity of the dihydroorotase of multienzymatic protein pyr1-3 from mouse Ehrlich ascites carcinoma.
Carcinoma, Ehrlich Tumor
Binding of radiolabeled N-(phosphonacetyl)-L-aspartate to aspartate transcarbamylase from Ehrlich ascites tumor cells.
Carcinoma, Hepatocellular
A multienzyme complex of carbamoyl-phosphate synthase (glutamine): aspartate carbamoyltransferase: dihydoorotase (rat ascites hepatoma cells and rat liver).
Carcinoma, Hepatocellular
Aspartate carbamoyltransferase inhibition and uridylate trapping result in a synergistic depression of uridine triphosphate in hepatoma cells.
Carcinoma, Hepatocellular
Feedback inhibition of aspartate transcarbamylase in liver and in hepatoma.
Carcinoma, Hepatocellular
Phosphorylation and dephosphorylation of carbamoyl-phosphate synthetase II complex of rat ascites hepatoma cells.
Carcinoma, Hepatocellular
Purification of homogeneous glutamine-dependent carbamyl phosphate synthetase from ascites hepatoma cells as a complex with aspartate transcarbamylase and dihydroorotase.
Colonic Neoplasms
Phase II trial of N-(phosphonacetyl)-L-aspartate (PALA), 5-fluorouracil and recombinant interferon-alpha-2b in patients with advanced gastric carcinoma.
Herpes Simplex
A continuous spectrophotometric assay for aspartate transcarbamylase and ATPases.
Hypothyroidism
Effect of hypothyroidism on aspartate transcarbamylase, uridine kinase, and DNA biosynthesis during cerebellar development in the rat.
hypoxanthine phosphoribosyltransferase deficiency
Elevated aspartate transcarbamylase and dihydroorotase activities in erythrocytes from patients with hypoxanthine guanine phosphoribosyltransferase deficiency.
Infections
Activity of some hepatic enzymes in schistosomiasis and concomitant alteration of arylsulfatase B.
Infections
Metabolic Reprogramming of Host Cells in Response to Enteroviral Infection.
Lesch-Nyhan Syndrome
Elevated aspartate transcarbamylase and dihydroorotase activities in erythrocytes from patients with hypoxanthine guanine phosphoribosyltransferase deficiency.
Leukemia
Inhibition of cell growth by N-(phosphonacetyl)-L-aspartate in human and murine cells in vitro.
Melanoma
Inhibition of cell growth by N-(phosphonacetyl)-L-aspartate in human and murine cells in vitro.
Melanoma
Kinetic parameters of aspartate transcarbamylase in human normal and tumoral cell lines.
Melanoma, Experimental
Inhibition of cell growth by N-(phosphonacetyl)-L-aspartate in human and murine cells in vitro.
Mycoses
The Asc locus for resistance to Alternaria stem canker in tomato does not encode the enzyme aspartate carbamoyltransferase.
Myocardial Infarction
Further heterogeneity demonstrated for serum creatine kinase isoenzyme MM.
Neoplasms
Activity of aspartate transcarbamylase in mammary tumours induced by 7,12-dimethyl-benzanthracene in the rat.
Neoplasms
Binding of radiolabeled N-(phosphonacetyl)-L-aspartate to aspartate transcarbamylase from Ehrlich ascites tumor cells.
Neoplasms
Diversion of aspartate in ASS1-deficient tumours fosters de novo pyrimidine synthesis.
Neoplasms
Effects of N-(phosphonacetyl)-L-aspartate on murine tumors and normal tissues in vivo and in vitro and the relationship of sensitivity to rate of proliferation and level of aspartate transcarbamylase.
Neoplasms
Flux through the de novo pyrimidine pathway in vivo. Effect of N-phosphonacetyl-L-aspartate, a potent inhibitor of aspartate transcarbamylase.
Neoplasms
Increased incidence of CAD gene amplification in tumorigenic rat lines as an indicator of genomic instability of neoplastic cells.
Neoplasms
Long-term association of N-(phosphonacetyl)-L-aspartate with bone.
Neoplasms
Mechanisms of sensitivity or resistance of murine tumors to N-(phosphonacetyl)-L-aspartate (PALA).
Neoplasms
N-(Phosphonacetyl)-L-aspartate inhibition of the enzyme complex of pyrimidine biosynthesis.
Neoplasms
New regulatory mechanism-based inhibitors of aspartate transcarbamoylase for potential anticancer drug development.
Neoplasms
Phase I study of N-(phosphonacetyl)-L-aspartic acid (PALA).
Neoplasms
Pyrimidine pathways enzymes in human tumors of brain and associated tissues: potentialities for the therapeutic use of N-(phosphonacetyl-L-aspartate and 1-beta-D-arabinofuranosylcytosine.
Neoplasms
Targeting pyrimidine synthesis accentuates molecular therapy response in glioblastoma stem cells.
Neoplasms
Urea Cycle Dysregulation Generates Clinically Relevant Genomic and Biochemical Signatures.
ornithine carbamoyltransferase deficiency
Expression, purification and kinetic characterization of wild-type human ornithine transcarbamylase and a recurrent mutant that produces 'late onset' hyperammonaemia.
Ornithine Carbamoyltransferase Deficiency Disease
Expression, purification and kinetic characterization of wild-type human ornithine transcarbamylase and a recurrent mutant that produces 'late onset' hyperammonaemia.
Pre-Eclampsia
Insulin-like growth factor binding protein-1 at the maternal-fetal interface and insulin-like growth factor-I, insulin-like growth factor-II, and insulin-like growth factor binding protein-1 in the circulation of women with severe preeclampsia.
Sarcoma, Yoshida
Intracellular distribution of various enzymes concerned with DNA synthesis from normal and regenerating rat liver, and Yoshida sarcoma.
Starvation
19F nuclear magnetic resonance studies of fluorotyrosine-labeled aspartate transcarbamoylase. Properties of the enzyme and its catalytic and regulatory subunits.
Starvation
CAD gene expression in serum-starved and serum-stimulated hamster cells.
Starvation
Characterization of a Salmonella typhimurium mutant defective in phosphoribosylpyrophosphate synthetase.
Starvation
Effects of phosphate limitation on expression of genes involved in pyrimidine synthesis and salvaging in Arabidopsis.
Starvation
The Escherichia coli K-12 "wild types" W3110 and MG1655 have an rph frameshift mutation that leads to pyrimidine starvation due to low pyrE expression levels.
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evolution
-
2 types of the enzyme occur: a CPSII-DHO-ATC fusion enzyme (CAD) found in animals, fungi, and amoebozoa, where the enzymes carbamoylphosphate synthetase II (CPSII), aspartate transcarbamoylase (ATC), and dihydroorotase (DHO), catalyzing the first three reaction steps of the de novo pyrimidine biosynthetic pathway, form a complex, and (2) stand-alone enzymes found in plants and the protist groups
evolution
in animals, CPSase, ATCase and DHOase are part of a 243 kDa multifunctional polypeptide named CAD
malfunction
analysis of the conformational changes shows that there is a lack of cooperativity in trimeric ATCases that do not possess regulatory subunits
malfunction
-
a missense mutation in the carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (cad) gene causes reduced lymphatic vessel development. The mutant also exhibits hyperbranching arteries, reminiscent of Notch pathway mutants. Notch signaling is significantly reduced in cadhu10125 mutants. hu10125 mutants display reduced formation of the thoracic duct and hyperbranched intersegmental arteries, penotype, overview
metabolism
-
the aspartate amino-N can be the source of nitrogen for glutamine synthesis by a substrate-channelled pathway which delivers glutamine to carbamoyl phosphate synthetase
metabolism
-
the binding of carbamoyl phosphate to the enzymes aspartate and ornithine transcarbamoylase reduces the rate of thermal decomposition of carbamoyl phosphate by a factor of >5000. Both of these transcarbamoylases use an ordered-binding mechanism in which carbamoyl phosphate binds first, allowing the formation of an enzyme-carbamoyl phosphate complex. The critical step in the thermal decomposition of carbamoyl phosphate in aqueous solution, in the absence of enzyme, involves the breaking of the C-O bond facilitated by intramolecular proton transfer from the amine to the phosphate. The binding of carbamoyl phosphate to the active sites of the enzymes significantly inhibits this process by restricting the accessible conformations of the bound ligand to those disfavoring the reactive geometry
metabolism
aspartate transcarbamoylase allosterically regulates pyrimidine nucleotide biosynthesis
metabolism
ATCase catalyzes one of the first reactions in pyrimidine nucleotide biosynthesis
metabolism
-
ATCase is an allosteric enzyme that catalyzes the committed step of pyrimidine nucleotide biosynthesis
metabolism
-
ATCase regulates the pyrimidine nucleotide biosynthesis by feedback control and by the cooperative binding of the substrate L-aspartate
metabolism
-
aspartate transcarbamoylase and dihydroorotase, enzymes that catalyze the second and third step in de novo pyrimidine biosynthesis, are associated in dodecameric complexes in Aquifex aeolicus and many other organisms, intersubunit communication in the dihydroorotase-aspartate transcarbamoylase complex of Aquifex aeolicus, overview. The architecture of the dodecamer is ideally suited to channel the intermediate, carbamoyl aspartate from its site of synthesis on the ATC subunit to the active site of dihydroorotase, which catalyzes the next step in the pathway, because both reactions occur within a large, internal solvent-filled cavity. The apparent second-order rate constant (kcat/Km) of ATC is 7.0fold greater than that of dihydroorotase
metabolism
-
the aspartate amino-N can be the source of nitrogen for glutamine synthesis by a substrate-channelled pathway which delivers glutamine to carbamoyl phosphate synthetase
-
physiological function
-
allosteric transition of ATCase, R-state stabilization by disulfide linkages, overview. Wild-type ATCase displays homotropic cooperativity with respect to the second substrate Asp due a shift from the low-activity, low-affinity T state to the high-activity, high-affinity R state
physiological function
aspartate transcarbamoylase allosterically regulates pyrimidine nucleotide biosynthesis
physiological function
-
ATCase catalyzes the committed step, the condensation of carbamoyl phosphate and aspartate to form carbamoyl aspartate and inorganic phosphate and regulates the pyrimidine nucleotide biosynthesis by feedback control and by the cooperative binding of the substrate L-aspartate, catalytic and regulatory mechanisms, overview. Each regulatory chain is also composed of two folding domains: the Zn domain, primarily involved in the binding of the zinc cofactor, and and the Al domain, primarily involved in the binding of allosteric effectors
physiological function
mechanisms of allosteric regulation in aspartate transcarbamoylase, overview
physiological function
-
the enzyme controls the rate of pyrimidine nucleotide biosynthesis by feedback inhibition, and helps to balance the pyrimidine and purine pools by competitive allosteric activation by ATP
physiological function
-
physically interacting with each other, carbamate kinase and ornithine carbamoyltransferase prevent thermodenaturation of carbamoyl phosphate (a precursor of pyrimidines and arginine, which is an extremely labile and potentially toxic intermediate) in the aqueous cytoplasmic environment. The carbamoyl phosphate channelling complex involves carbamate kinase, ornithine carbamoyltransferase and aspartate carbamoyltransferase
physiological function
the enzyme catalyzes the first step in the pyrimidine biosynthetic pathway
physiological function
-
CAD protein, formed by carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotase, is a multifunctional enzyme required for the de novo synthesis of pyrimidine nucleotides. Aspartate transcarbamoylase is located at the C-terminal part of CAD, Each activity is coded in a separate domain
physiological function
-
carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase form the CAD complex that is essential for UDP biosynthesis, which is necessary for protein glycosylation and de novo biosynthesis of pyrimidine-based nucleotides. CAD is an unappreciated mechanism that regulates Notch/Vegf signaling during angiogenesis
physiological function
enzyme aspartate transcarbamoylase catalyzes the committed step in pyrimidine nucleotide biosynthesis and allosterically regulates the pathway in Escherichia coli
physiological function
upregulation of CAD, comprising CPSase, ATCase and DHOase activities, is essential for normal and tumour cell proliferation
physiological function
-
the enzyme catalyzes the first step in the pyrimidine biosynthetic pathway
-
physiological function
-
physically interacting with each other, carbamate kinase and ornithine carbamoyltransferase prevent thermodenaturation of carbamoyl phosphate (a precursor of pyrimidines and arginine, which is an extremely labile and potentially toxic intermediate) in the aqueous cytoplasmic environment. The carbamoyl phosphate channelling complex involves carbamate kinase, ornithine carbamoyltransferase and aspartate carbamoyltransferase
-
additional information
-
allosteric and kinetic structures, overview
additional information
allosteric transition between the T and R enzyme states
additional information
-
importance of intradomain and intrachain interactions for the different comformational states, T and R states, active site and allosteric site structure, overview. Important for the stability of the T state are the Glu239c1 interaction with both Lys164c4 and Tyr165c4, the Asp236c1 interaction with Lys143r4, and the Ser238c1 interaction with Asn111r4. In the R state, Glu239c1 forms new interchain interactions with Lys164c1 and Tyr165c1, while Asn111r4 forms a new interaction with Glu109c4
additional information
nucleotide binding site specificity conformational changes due to nucleotide binding, overview
additional information
-
nucleotide binding site specificity conformational changes due to nucleotide binding, overview
additional information
-
Rheb binds CAD in a GTP- and effector domain-dependent manner. The region of CAD where Rheb binds is located at the C-terminal region of the carbamoyl-phosphate synthetase domain and not in the dihydroorotase and aspartate transcarbamoylase domains. Rheb stimulated carbamoyl-phosphate synthetase activity of CAD in vitro. CAD binding is more pronounced with Rheb2 than with Rheb1
additional information
-
the dihydroorotase loop A that binds between the two ATC domains is an allosteric or noncompletive ATC inhibitor with Ki 5 of 0.022 mM, loop A is an important component of the functional linkage between the enzymes. modeling, overview
additional information
three-dimensional enzyme homology structure modeling using the crystal structure of ATCase from Pyrococcus abyssi, PDB ID:1ML4, molecular dynamics simulations and enzyme conformation stability, ligand binding study, overview. The residues Thr53, Arg104, and Gln219 are consistently involved in strong hydrogen-bonding interactions and play a vital role in the TtATCase activity
additional information
-
three-dimensional enzyme homology structure modeling using the crystal structure of ATCase from Pyrococcus abyssi, PDB ID:1ML4, molecular dynamics simulations and enzyme conformation stability, ligand binding study, overview. The residues Thr53, Arg104, and Gln219 are consistently involved in strong hydrogen-bonding interactions and play a vital role in the TtATCase activity
-
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complex of aspartate transcarbamoylase and dihydroorotase
noncovalent hexamer of dihydroorotase and ATCase, to 2.3 A resolution. The structure has citrate, bound to the active sites of both enzymes.Six DHO and six ATC chains form a hollow dodecamer, in which the 12 active sites face an internal reaction chamber that is approximately 60 A in diameter and connected to the cytosol by narrow tunnels. The entrances and the interior of the chamber are both electropositive, which suggests that the architecture of this nanoreactor modifies the kinetics of the bisynthase, not only by steric channeling but also by preferential escape of the product, dihydroorotase
50 mM Tis-HCl, pH 8.1, 70% ammonium sulfate
-
purified recombinant enzyme alone or complex with substrate carbamoyl phosphate or inhibitor N-phosphonacetyl-L-aspartate, hanging drop vapor diffusion method, 12 mg/ml protein is mixed with an equal volume of crystallization buffer containing 1.7 M (NH4)2SO4, 0.1 M Tris-HCl, pH 8.5, and 2.0% PEG 200, and equilibratopn over a reservoir of 0.5 ml of crystallization buffer at 20°C, 1 week, for substrate bound enzyme the crystals are soaked in mother liquor containing the ligand at 13.3 mM, for inhibitor bound form, the enzyme is crystallized as described using crystallization buffer containing 0.1 M potassium bromide, 0.1 M N-cyclohexyl-3-aminopropanesulfonic acid, pH 10.0, and 18% PEG 8000, 20°C, 1 week, X-ray diffraction structure determination and analysis at 2.1-2.6 A resolution
approx. 30% ammonium sulfate, crystals appear after about 2 weeks at 4°C
-
ATCase locked in the R quaternary structure by specific introduction of disulfide bonds bound to the final product molecule phosphate, 10 mg/ml protein solution is dialyzed against a solution of 100 mM potassium dihydrogen phosphate and 3 mM sodium azide, pH 5.9, 1 week, X-ray diffraction structure determination and analysis at 2.85 A resolution, molecular replacement
-
bound to N-phosphonacetyl-L-aspartate, citrate or phosphate, crystalline R-state P212121
-
cocrystallization of catalytic subunit with N-(phosphonoacetyl)-L-aspartate by vapor diffusion, crystals grow from 0.005 ml of 100 mM Tris-HCl, pH 6.8, 20 mM calcium acetate, 5.8% polyethylene glycol 8000 and 0.005 ml of catalytic subunit in 10 mM Tris-HCl, pH 7.5, 1 mM 2-mercaptoethanol and 2 mM N-(phosphonoacetyl)-L-aspartate
hanging drop vapor diffusion method, using 0.1 M MES, pH 6.0, 10% (v/v) glycerol, and 10% (w/v) PEG 8000
hanging drop vapor diffusion method, using 0.2 m NH4Ac, 0.1 m Tris pH 8.5, 20% (w/v) PEG3350, and 10% glycerol for all enzyme mutants, and 0.1 m HEPES pH 7.0, 30% (w/v) Jeffamine M-600 pH 7.0, and 10% (v/v) glycerol for all enzyme holo mutants
hanging drop vapor diffusion, X-ray structure of unliganded ATCase at pH 8.5
-
microdialysis method, structure of D236A ATCase in the presence of phosphonoactamide and Asp
-
mutant E50A, in presence of phosphonoacetamide and malonate to trap the enzyme in T-like and R-like structures
-
mutant K244N, loss of numerous local T-state stabilizing interactions
-
purified recombinant ATCase in complex with UTP, CTP, or dCTP, dialysis of 20 mg/ml protein against 40 mM sodium citrate, 1 mM 2-mercaptoethanol, 0.2 mM EDTA, and 1.0 mM CTP, pH 5.7, at 20°C, 1 week, transfer of dialysis buttons to 2 mL of crystallization buffer with 5 mM UTP and 5 mM MgCl2 and equilibration for 12 h, and to crystallization buffer containing 5 mM UTP and 5 mM MgCl2 for 12 h, respectively, cryoprotection in 20% 2-methyl-2,4-pentanediol in UTP-Mg2+ crystallization buffer, X-ray diffraction structure determination and analysis at 1.9-2.1 A resolution
purified recombinant enzyme, 20 mg/ml protein is mixed with 40 mM sodium citrate, 1 mM 2-mercaptoethanol, 0.2 mM EDTA, and 1.0 mM CTP, pH 5.7, at 20 °C, 1 week, X-ray diffraction structure determination and analysis at 2.1 A resolution
purified recombinant mutant enzyme K164E/E239K, mixing of 10 mg/ml enzyme in 50 mM Tris-acetate, pH 8.3, with 0.002 ml of crystallization buffer containing 16% w/v PEG 4000, 0.04 M Na2MoO4-2H2O, 0.04 M N-cyclohexyl-3-aminopropanesulfonic acid, and 30 mM Tris-acetate, pH 8.75, and equilibration over a reservoir of crystallization buffer of 1.0 ml, 20°C, 2 weeks, X-ray diffraction structure determination and analysis
series of X-ray crystal structures of the enzyme in the presence and absence of substrates, products, and analogues, structure analysis, detailed overview. The structure of the enzyme in the presence of citrate, an analogue of N-carbamoyl-L-aspartate plus the product phosphatewas determined after displacement of N-phosphonacetyl-L-aspartate from R-state crystals
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use of Methyl-TROSY spectra for assignment for approximately 60% of the observed methyl groups in TROSY maps of ATCase by the divide and conquer method. The combination of all approaches leads to assignments for 86% of the methyl groups, providing a large number of probes of structure and dynamics. The derived assignments are used to interpret chemical shift changes of ATCase upon titration with the nucleotide ATP. Large shift changes in the N-terminal tails of the regulatory chain provide the first evidence for structural perturbations in a region playing a critical role on the effect of nucleotide binding on distal catalytic sites of the allosteric enzyme
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X-ray crystal structure of the N-phosphonacetyl-L-asparagine complexed with ATCase. Analysis of the crystal structure of the enzyme in the presence of N-phosphonacetyl-L-asparagine reveals that the binding of N-phosphonacetyl-L-asparagine is similar to that of the R-state complex of ATCase with N-phosphonaceyl-L-aspartate, another potent inhibitor of the enzyme
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X-ray structure at 5.5 A resolution
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X-ray structure of the holoenzyme in the presence of the substrate analog N-phosphonoacetyl-L-aspartate, carbamoylphosphate and succinate
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X-ray structures of wild-type Escherichia coli aspartate transcarbamoylase holoenzyme and catalytic subunit crystallized with different ligands, overview
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free enzyme and bound to carbamoyl phosphate or N-phosphonacetyl-L-aspartate
purified detagged isolated recombinant huATCase, free or in complex with inhibitor N-phosphonoacetyl-L-aspartate, 1.5 mg/ml protein, 0.1 M Tris pH 8.5, 6% PEG 8000, and 9% ethylene glycol is mixed with 0.1 M CAPS pH 10, 150 mM NaCl or 1.5 mg ml1 and 10 mM ZnCl2, 15% PEG 6000, 50 mM sodium acetate pH 4.8, and 0.5 mM inhibitor, X-ray diffraction structure determination and analysis at 2.1 A resolution
catalytic chain in the presence of the regulatory chain in the hexagonal space group P6322, with one monomer per asymmetric unit, sitting drop vapor diffusion method, mixing of 0.0013 protein-ligand solution, containing 11 mg/ml protein in 50 mM Tris, pH 8.3, 150 mM NaCl, 2 mM BME, 0.05 mM zinc acetate, with 0.001 ml of reservoir solution containing 2.0 M ammonium sulfate, 0.2 M potassium sodium tartrate tetrahydrate, 0.1 M sodium citrate tribasic dihydrate, pH 5.6, or 2.0 M ammonium sulfate, 0.2 M potassium sodium tartrate tetrahydrate, 0.1 M Tris-HCl, pH 7.5, 22°C, X-ray diffraction structure determination and analysis at 2.50 A resolution, molecular replacement
crystals are grown at 295 K by the sitting-drop method from reservoirs containing 2.0 M ammonium sulfate and 5% 2-propanol. The catalytic trimer is crystallized in space group R32, with unit-cell parameters a = b = 265.3, c = 195.5 A and two trimers in the asymmetric unit. Its structure is determined using molecular replacement and Patterson methods
crystals of the catalytic subunit in an orthorhombic crystal form contain four crystallographically independent trimers which associate in pairs to form stable staggered complexes. Each subunit has a sulfate in the central channel. The catalytic subunits in these complexes show flexibility, with the elbow angles of the monomers differing by up to 7.4° between crystal forms. There is also flexibility in the relative orientation of the trimers around their threefold axis in the complexes, with a difference of 4° between crystal forms
sitting drop method, crystal structure of the catalytic trimer
3 catalytic and 3 regulatory subunits per asymmetric unit
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the crystal structure of the unliganded Moritella profunda ATCase shows resemblance to a more extreme T state reported previously for an Escherichia coli ATCase mutant
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full-length enzyme, sitting drop vapor diffusion method, using 0.2 M potassium citrate tribasic monohydrate, 20% (w/v) PEG 3350. Enzyme in complex with 2,3-naphthalenediol, hanging drop vapor diffusion method, 0.1 M bis-Tris propane pH 7.5, 0.2 M Na2SO4, 15% (w/v) PEG 3350
truncated enzyme, hanging drop vapor diffusion method, using 0.2 M sodium sulfate, 5 mM MgSO4, 15% (w/v) PEG 3350 in 0.1 M bis-Tris propane pH 7.5
hanging drop method, equal volumes of 1 mg/ml enzyme in 100 mM Tris-HCl, pH 8.5 is mixed with 100 mM citrate, pH 5, and 10% 6K polyethylene glycol
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hanging-drop vapour-diffusion, 0.002 ml of enzyme solution, 7 mg/ml, in 20 mM Tris-HCl, pH 8.2, 2 mM 2-mercaptoethanol, 300 mM NaCl, is mixed with 0.002 ml reservoir solution consisting of 1.4 M citrate, pH 6.8, X-ray structure to 1.8 A resolution
aspartate carbamoyltransferase in complex with its allosteric activator CTP
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hanging drop vapour-diffusion technique at 20°C. Tertiary and quaternary structure of the T state ATCase of the enzyme determined by X-ray crystallography to 2.6 A resolution
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in ligand free form and in complex with carbamoyl phosphate to 2.8 A and to 1.6 A resolution, respectively. Presence of two homotrimers in the asymmetric unit
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A241C
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reduced affinity for aspartate, hyperbolic aspartate saturation curve
C47A
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Hill coefficient 1.3 as compared to 2.4 for wild-type
D162A
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7700fold reduction in specific activity, 2fold decrease in affinity for aspartate, loss of homotropic cooperativity and decreased activation by ATP
E239Q
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mutation in the catalytic subunit, the mutation substantially destabilize the T state of the enzyme
G128A
the mutation completely abolishes enzyme activity
G128A/G130A
the mutation completely abolishes enzyme activity
G166A
the mutant retains some activity
G166P
the mutant loses almost all activity
H107A
the mutant shows reduced activity compared to the wild type enzyme
H107A/Y197A
the mutant shows reduced activity compared to the wild type enzyme
K143A
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mutation in the regulatory subunit, the mutation substantially destabilize the T state of the enzyme
K164E/E239K
site-directed mutagenesis, a mutant aspartate transcarbamoylase exists in an intermediate quaternary structure between the canonical T and R structures, crystal structure and quaternary conformation analysis, detailed overview. pH-Dependent structural alteration consistent with either a pH-induced conformational change or a pH-induced alteration in the T to R equilibrium
K244A
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dramatic reduction in homotropic cooperativity and the ability of heterotropic effectors to modulate activity
K244N
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dramatic reduction in homotropic cooperativity and the ability of heterotropic effectors to modulate activity
K60A
a regulatory mutant, which does not exhibit UTP synergistic inhibition
K6A
a regulatory mutant, which does not exhibit UTP synergistic inhibition
L151Q
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strongly reduced stimulation by ATP, synergistic inhibition by UTP is decreased
L151V
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stimulation by ATP is reduced by 50%
L32A
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stimulation by ATP is reduced by 25%
L76A
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synergistic inhibition by UTP is decreased
L7A
a regulatory mutant, which does not exhibit UTP synergistic inhibition
N111A
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mutation in the regulatory subunit, the mutation substantially destabilize the T state of the enzyme
P268A
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40fold reduction in activity, concentration of N-(phosphonoacetyl)-L-aspartate for maximal activation is increased 233fold as compared to the wild-type, less activation by ATP, stronger inhibition by CTP
Q73E
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stimulation by ATP is reduced by 80%
R105A
catalytic trimer mutant
V106A
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synergistic inhibition by UTP is decreased
V106W
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strongly reduced stimulation by ATP
V106W/Y77F
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strongly reduced stimulation by ATP
Y165F
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mutant enzyme shows greatly reduced affinity for aspartate and activity
Y197A
the mutant shows reduced activity compared to the wild type enzyme
Y197F
the mutant shows reduced activity compared to the wild type enzyme
Y240F
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mutant enzyme shows higher affinity for aspartate and increased activity
Y77F
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synergistic inhibition by UTP is decreased
D1958A
the mutant shows 2.5fold reduced activity compared to the wild type enzyme
E1954A
the mutant shows 4fold reduced activity compared to the wild type enzyme
G128A/G130A
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the mutant loses almost all activity
G130A
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the mutant retains some activity
G132A
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the mutation completely abolishes enzyme activity
G166A
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the mutant retains some activity
G166P
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the mutant loses almost all activity
R2024Q
the mutation virtually inactivates the enzyme, reducing the activity about 1000fold
R109A/K138A
the mutant shows significantly lower activity compared to the wild type enzyme
C47A/A241C
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non-reducing conditions, reduced affinity for aspartate, hyperbolic aspartate saturation curve
C47A/A241C
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the mutant holoenzyme with disulfides intact displays a hyperbolic Asp saturation curve confirming the loss of homotropic cooperativity, phosphate binding structure of the mutant, overview
D19A
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loss of the synergistic inhibition of UTP in the presence of CTP
D19A
a regulatory mutant, which does not exhibit UTP synergistic inhibition
D236A
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the small-angle x-ray scattering pattern of unliganded D236A ATCase differs from the scattering pattern of the wild-type enzyme
D236A
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mutation in the catalytic subunit, the mutation substantially destabilize the T state of the enzyme
D236A
site-directed mutagenesis, the wild-type enzyme shows o change in structure by SAXS through the temperature range of 4°C to 55°C, whereas the D236A ATCase exhibits a large shift toward the T state between 4°C and 30°C, with a minor shift back toward the R state between 30°C and 45°C
E50A
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mutant enzyme shows a low activity, low affinity state, only 2fold activation with N-(phosphonoacetyl)-L-aspartate, kinetic mechanism is changed
E50A
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shift of equilibrium toward unliganded T-state, crystallization analysis
H20A
a regulatory mutant, which does not exhibit UTP synergistic inhibition
H20A
the mutation results in the complete loss of synergistic inhibition by UTP
K56A
a regulatory mutant, which does not exhibit UTP synergistic inhibition
K56A
the mutation results in the complete loss of synergistic inhibition by UTP
Q137A
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no induction of induced fit by substrates, enzyme is lockd in the low-activity, low affinity T-state
Q137A
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the concentration of carbamoyl phosphate required to attain one half of the maximal activity increases by 210fold, the corresponding value for aspartate increases by 76fold, extremely reduced affinity for carbamoyl phosphate and near abolition of aspartate binding compared to the wild-type enzyme
R167A
inactive
R167A
the mutation completely abolishes enzyme activity
additional information
in noncovalent association with dihydroorotase, possible model for mammalian polypeptide chain CPSase/ATCase/DHOase during pyrimidine biosynthesis
additional information
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in noncovalent association with dihydroorotase, possible model for mammalian polypeptide chain CPSase/ATCase/DHOase during pyrimidine biosynthesis
additional information
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chimeric enzyme consisting of E.coli catalytic subunit and Serratia marcescens regulatory subunit
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