Literature summary for 6.4.1.2 extracted from

Zhang, H.; Tweel, B.; Li, J.; Tong, L.
Crystal structure of the carboxyltransferase domain of acetyl-coenzyme A carboxylase in complex with CP-640186 (2004), Structure, 12, 1683-1691.

Activating Compound

Activating Compound	Comment	Organism	Structure
biotin	-	Homo sapiens
biotin	-	Saccharomyces cerevisiae

Application

Application	Comment	Organism
drug development	the structure of the enzyme's active site can be used for drug discovery	Saccharomyces cerevisiae

Cloned(Commentary)

Cloned (Comment)	Organism
expression of the His-tagged carboxyltransferase domain comprising residues 1548-2346 in Escherichia coli	Homo sapiens

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified recombinant carboxyltransferase domain comprising residues 1476-2233 in complex with CP-640186, hanging drop vapour diffusion method, crystallization of the free enzyme in a 10 mg/ml solution using a reservoir solution containing 0.1 M sodium citrate, pH 5.5, 0.2 M NaCl, 8% w/v PEG 8000, and 10% v/v glycerol, soaking of the crystals in 1 mM inhibitor CP-640186, X-ray diffraction structure determination and analyis at 2.8 A resolution	Saccharomyces cerevisiae

Crystallization (Comment)

Organism

purified recombinant carboxyltransferase domain comprising residues 1476-2233 in complex with CP-640186, hanging drop vapour diffusion method, crystallization of the free enzyme in a 10 mg/ml solution using a reservoir solution containing 0.1 M sodium citrate, pH 5.5, 0.2 M NaCl, 8% w/v PEG 8000, and 10% v/v glycerol, soaking of the crystals in 1 mM inhibitor CP-640186, X-ray diffraction structure determination and analyis at 2.8 A resolution

Saccharomyces cerevisiae

Inhibitors

Inhibitors	Comment	Organism
CP-640186	herbicide, noncompetititve to malonyl-CoA, molecular inhibitory mechanism, binding structure, binds to the biotin binding site	Homo sapiens
CP-640186	herbicide, IC50 is 0.008 mM, noncompetititve to malonyl-CoA, molecular inhibitory mechanism, binding structure involving Leu1705 and Val1967, binds to the biotin binding site	Saccharomyces cerevisiae
CP-640188	molecular inhibitory mechanism, binding structure	Homo sapiens
Haloxyfop	herbicide, binding structure and inhibition mechanism, binds to an allosteric site	Saccharomyces cerevisiae

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
ATP + acetyl-CoA + HCO3-	Homo sapiens	-	ADP + malonyl-CoA + phosphate	-	?
ATP + acetyl-CoA + HCO3-	Saccharomyces cerevisiae	-	ADP + malonyl-CoA + phosphate	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-
Saccharomyces cerevisiae	-	-	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant His-tagged carboxyltransferase domain comprising residues 1548-2346 from Escherichia coli by nickel affinity and ion exchange chromatography	Homo sapiens

Reaction

Reaction	Comment	Organism	Reaction ID
ATP + acetyl-CoA + hydrogencarbonate = ADP + phosphate + malonyl-CoA	molecular surface of the active site of the carboxyltransferase domain	Saccharomyces cerevisiae	a

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
ATP + acetyl-CoA + HCO3-	-	Homo sapiens	ADP + malonyl-CoA + phosphate	-	?
ATP + acetyl-CoA + HCO3-	-	Saccharomyces cerevisiae	ADP + malonyl-CoA + phosphate	-	?

Synonyms

Synonyms	Comment	Organism
ACC	-	Saccharomyces cerevisiae
ACC1	-	Homo sapiens

Cofactor

Cofactor	Comment	Organism	Structure
ATP	-	Homo sapiens
ATP	-	Saccharomyces cerevisiae

Ki Value [mM]

Ki Value [mM]	Ki Value maximum [mM]	Inhibitor	Comment	Organism
additional information	-	additional information	kinetics	Saccharomyces cerevisiae
additional information	-	additional information	dissociation constants of inhibitors CP-640186 and CP-640188	Homo sapiens
0.0049	-	CP-640186	-	Saccharomyces cerevisiae

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor	Structure
0.008	-	herbicide, IC50 is 0.008 mM, noncompetititve to malonyl-CoA, molecular inhibitory mechanism, binding structure involving Leu1705 and Val1967, binds to the biotin binding site	Saccharomyces cerevisiae	CP-640186