The G553M mutant of peroxisomal carnitine octanoyltransferase catalyses acetyl transfer and acetyl-CoA hydrolysis

N Sitheswaran, N T Price, R R Ramsay

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

The structure of carnitine acetyltransferase revealed a putative binding site for longer acyl chains but access was blocked by methionine 564 (G. Jogl and L. Tong (2003) Cell 112, 113-122). The equivalent residue in all long chain carnitine acyltransferases is a conserved glycine. Mutation of glycine 553 to methionine in bovine COT resulted in loss of activity with all acyl-CoA substrates except acetyl-CoA, supporting the hypothesis that the methionine blocks access for longer acyl chains. The kinetic characteristics of acetyl transfer to carnitine were identical in the native and mutant enzyme. However, rapid acetyl-CoA hydrolysis in the mutant but not the wild-type indicates perturbation of the catalytic site.

Original languageEnglish
Pages (from-to)1341-1347
Number of pages7
JournalMonatshefte für Chemie
Volume136
DOIs
Publication statusPublished - Aug 2005

Keywords

  • carnitine
  • substrate specificity
  • acetyl-coenzyme A
  • site-directed mutagenesis
  • altered catalysis
  • SUBSTRATE SELECTIVITY
  • CRYSTAL-STRUCTURE
  • ACETYLTRANSFERASE
  • PALMITOYLTRANSFERASE
  • ENZYMOLOGY
  • TRANSPORT
  • MECHANISM

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