EC Number |
General Information |
Reference |
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2.1.1.292 | evolution |
phylogenetic analysis of the putative SAM-dependent methyltransferases reveals our distinct clades, which are composed of DnrK and RdmB-type proteins and two other groups of sequences. Evolution of anthracycline methyltransferase-like proteins, the phylogenetic analysis suggests that the functional divergence of these proteins has occurred in situ in their respective gene clusters, overview |
755690 |
2.1.1.292 | evolution |
the 10-decarboxylation activity of DnrK is the basis of evolution of a RdmB (aclacinomycin 10-hydroxylase RdmB, EC 3.1.1.95, UniProt ID Q54527), an atypical 10-hydroxylase that requires SAM of the rhodomycin pathways, which has 10-hydroxylation ability. Structural comparisons of DnrK and RdmB. phylogenetic tree and substrate specificities, overview |
758220 |
2.1.1.292 | malfunction |
insertion of a single serine residue to DnrK is sufficient for introduction of a monooxygenation activity. The inserted serine S297 resides in an alpha-helical segment adjacent to the substrate, but in a manner where the side chain points away from the active site. The shift in activity is mediated by rotation of a preceding phenylalanine F296 toward the active site, which blocks a channel to the surface of the protein that is present in native DnrK |
758220 |
2.1.1.292 | metabolism |
both DnrK and RdmB are postulated to catalyze the decarboxylation of 15-demethoxy-aclacinomycin T as a first step. In DnrK, the open active site allows protonation of the resulting carbanion by solvent molecules and 4-O-methylation to generate 4-O-methyl-15-decarboxyaclacinomycin T. In contrast, RdmB stabilizes the carbanion and catalyzes the formation of an O2-anthracycline caged radical pair in the closed active site. Consequent formation of a peroxyl intermediate and subsequent reduction of the peroxide by intracellular thiols possibly outside the active site of the enzyme yields the 10-hydroxylated product 11-deoxy-beta-rhodomycin T. The reaction sequence leading to the double-product 4-O-methyl-11-deoxy-beta-rhodomycin T is only possible if the RdmB reaction happens first. R1, L-rhodosamine. Formation of the DnrK/RdmB double-reaction product 4-O-methyl-11-deoxy-beta-rhodomycin T must proceed through initial 10-hydroxylation followed by 4-O-methylation |
758220 |
2.1.1.292 | metabolism |
the S-adenosyl methionine (SAM)-dependent methyltransferase DnrK is a 4-O-methyltransferase involved in daunorubicin biosynthesis |
755690 |
2.1.1.292 | more |
the substrate binding site is formed between the C-terminal domain, which has a Rossmann-like alpha/beta-fold typical to nucleotide-binding proteins, and the middle domain |
758220 |
2.1.1.292 | physiological function |
methyltransferase DnrK is a true methyltransferase that catalyzes the 4-O-methylation of carminomycin in one of the final steps in the biosynthesis of the antitumor drug daunorubicin in Streptomyces peucetius. The enzyme possesses rather relaxed substrate specificity in regard to modifications in the polyaromatic anthracycline ring system, but it is quite specific with respect to the length of the carbohydrate chain at C-7, accepting only monoglycosides. In addition, DnrK has even been shown to be able to methylate various flavonoids |
758220 |
2.1.1.292 | physiological function |
the enzyme catalyzes the terminal enzymic step in the formation of daunomycin |
722879 |
2.1.1.292 | physiological function |
the enzyme is involved in daunorubicin biosynthesis |
722641 |
2.1.1.292 | physiological function |
the prototypical class I MT DnrK is a model and is the carminomycin 4-O-ethyltransferase that catalyzes a culminating step in the biosynthesis of the anticancer agent daunorubicin in Streptomyces peucetius |
755675 |