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). a (2S)-2-methylacyl-CoA = a (2R)-2-methylacyl-CoA (2S)-2-methyltetradecanoyl-CoA = (2R)-2-methyltetradecanoyl-CoA (2R)-pristanoyl-CoA = (2S)-pristanoyl-CoA (25S)-3-oxocholest-4-en-26-oyl-CoA = (25R)-3-oxocholest-4-en-26-oyl-CoA (2S)-ibuprofenoyl-CoA = (2R)-ibuprofenoyl-CoA Inactivated by N,N-dialkylcarbamoyl-CoA substrate-product analogs. 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). Homodimer. 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. Interconversion is achieved via a planar enolate intermediate. Belongs to the CoA-transferase III family.