UniProt functional annotation for O06543

UniProt code: O06543.

Organism: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
Taxonomy: Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae; Mycobacterium; Mycobacterium tuberculosis complex.
 
Function: Catalyzes the epimerization of (2R)- and (2S)-methylacyl- coenzyme A (CoA) thioesters (PubMed:15632186, PubMed:19854148, PubMed:26348625). Accepts as substrates a wide range of alpha- methylacyl-CoAs, including (2R)-2-methylmyristoyl-CoA and (2S)-2- methylmyristoyl-CoA, (2R)-pristanoyl-CoA and (2S)-pristanoyl-CoA, and the cholesterol esters (25R)-3-oxo-cholest-4-en-26-oyl-CoA and (25S)-3- oxo-cholest-4-en-26-oyl-CoA (PubMed:15632186, PubMed:26348625). Can also catalyze the interconversion of the non-physiologic substrates (2R)-ibuprofenoyl-CoA and (2S)-ibuprofenoyl-CoA, which are potential competitive inhibitors of the enzyme (PubMed:19854148). {ECO:0000269|PubMed:15632186, ECO:0000269|PubMed:19854148, ECO:0000269|PubMed:26348625}.
 
Catalytic activity: Reaction=a (2S)-2-methylacyl-CoA = a (2R)-2-methylacyl-CoA; Xref=Rhea:RHEA:12657, ChEBI:CHEBI:57313, ChEBI:CHEBI:57314; EC=5.1.99.4; Evidence={ECO:0000269|PubMed:15632186};
Catalytic activity: Reaction=(2S)-2-methyltetradecanoyl-CoA = (2R)-2-methyltetradecanoyl- CoA; Xref=Rhea:RHEA:46724, ChEBI:CHEBI:86520, ChEBI:CHEBI:86521; Evidence={ECO:0000269|PubMed:15632186};
Catalytic activity: Reaction=(2R)-pristanoyl-CoA = (2S)-pristanoyl-CoA; Xref=Rhea:RHEA:40447, ChEBI:CHEBI:77099, ChEBI:CHEBI:77275; Evidence={ECO:0000269|PubMed:15632186};
Catalytic activity: Reaction=(25S)-3-oxocholest-4-en-26-oyl-CoA = (25R)-3-oxocholest-4-en- 26-oyl-CoA; Xref=Rhea:RHEA:63172, ChEBI:CHEBI:83819, ChEBI:CHEBI:146202; Evidence={ECO:0000269|PubMed:26348625};
Catalytic activity: Reaction=(2S)-ibuprofenoyl-CoA = (2R)-ibuprofenoyl-CoA; Xref=Rhea:RHEA:63176, ChEBI:CHEBI:146203, ChEBI:CHEBI:146204; Evidence={ECO:0000269|PubMed:19854148};
Activity regulation: Inactivated by N,N-dialkylcarbamoyl-CoA substrate- product analogs. {ECO:0000269|PubMed:29502025}.
Biophysicochemical properties: Kinetic parameters: KM=41 uM for (R)-pristanoyl-CoA {ECO:0000269|PubMed:15632186}; KM=6.5 uM for (25R)-3-oxo-cholest-4-en-26-oyl-CoA {ECO:0000269|PubMed:26348625}; KM=86 uM for (2S)-ibuprofenoyl-CoA {ECO:0000269|PubMed:19854148}; KM=48 uM for (2R)-ibuprofenoyl-CoA {ECO:0000269|PubMed:19854148}; Vmax=214 umol/min/mg enzyme with (R)-pristanoyl-CoA as substrate {ECO:0000269|PubMed:15632186}; Note=kcat is 3.7 sec(-1) with (25R)-3-oxo-cholest-4-en-26-oyl-CoA as substrate (PubMed:26348625). kcat is 450 sec(-1) with (2S)- ibuprofenoyl-CoA as substrate (PubMed:19854148). kcat is 291 sec(-1) with (2R)-ibuprofenoyl-CoA as substrate (PubMed:19854148). {ECO:0000269|PubMed:19854148, ECO:0000269|PubMed:26348625};
Subunit: Homodimer. {ECO:0000269|PubMed:12554951, ECO:0000269|PubMed:15632186}.
Biotechnology: Development of gem-disubstituted substrate-product analogs as inhibitors of racemases and epimerases is elaborated using alpha-methylacyl-CoA racemase from Mycobacterium tuberculosis as a model enzyme. These non-physiologic substrates could be used as a therapeutic agent to inhibit human AMACR, which is overexpressed in prostate cancer. {ECO:0000269|PubMed:29502025}.
Miscellaneous: Interconversion is achieved via a planar enolate intermediate. {ECO:0000269|PubMed:22360758}.
Similarity: Belongs to the CoA-transferase III family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.