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)

Chem Commun (Camb). 2014 Nov 25;50(91):14164-6. doi: 10.1039/c4cc06127f.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl Coenzyme A / chemistry
  • Acyl Coenzyme A / metabolism*
  • Biocatalysis*
  • Fluorides / chemistry
  • Fluorides / metabolism*
  • Humans
  • Molecular Conformation
  • Racemases and Epimerases / chemistry
  • Racemases and Epimerases / metabolism*

Substances

  • Acyl Coenzyme A
  • Racemases and Epimerases
  • alpha-methylacyl-CoA racemase
  • Fluorides