title: The perils of rational design--unexpected irreversible elimination of fluoride from 3-fluoro-2-methylacyl-CoA esters catalysed by α-methylacyl-CoA racemase (AMACR; P504S).
abstract: α-Methylacyl-CoA racemase (AMACR; P504S) catalyses 'racemization' of 2-methylacyl-CoAs, the activation of R-ibuprofen and is a promising cancer drug target. Human recombinant AMACR 1A catalyses elimination of 3-fluoro-2-methyldecanoyl-CoAs to give E-2-methyldec-2-enoyl-CoA and fluoride anion, a previously unknown reaction. 'Racemization' of 2-methyldec-3-enoyl-CoAs was also catalysed, without double bond migration.
authors.affiliation: Medicinal Chemistry, Department of Pharmacy & Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY, UK. M.D.Lloyd@bath.ac.uk.
authors.forename: Maksims
authors.initials: M
authors.lastname: Yevglevskis
authors.forename: Guat L
authors.initials: GL
authors.lastname: Lee
authors.forename: Michael D
authors.initials: MD
authors.lastname: Threadgill
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Woodman
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Lloyd
mesh_terms: D000214:Acyl Coenzyme A / Q000737:chemistry / Q000378:metabolism*; D055162:Biocatalysis; D005459:Fluorides / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008968:Molecular Conformation; D019998:Racemases and Epimerases / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000214:Acyl Coenzyme A; D019998:Racemases and Epimerases; C108352:alpha-methylacyl-CoA racemase; D005459:Fluorides