The mouse gene PDCR encodes a peroxisomal Δ24-dienoyl-CoA reductase

Brian V. Geisbrecht, Xiquan Liang, James C. Morrell, Horst Schulz, Stephen J. Gould

Research output: Contribution to journalArticlepeer-review

Abstract

Here we describe the identification and characterization of a novel mouse gene, PDCR, that encodes a peroxisomal Δ24-dienoyl-CoA reductase. The mouse PDCR cDNA contains an 892-base pair open reading frame and is predicted to encode a 292-amino acid protein with a deduced molecular mass of 31,298 Da that terminates in a consensus type-1 peroxisomal targeting signal. Purified recombinant PDCR protein was generated from Escherichia coli and catalyzed the NADPH-dependent reduction of Δ2-trans,Δ4-trans-decadienoyl- CoA with a specific activity of 20 units/mg. Enzymatic characterization followed by high pressure liquid chromatography analysis of the products revealed that PDCR converted Δ2-trans,Δ4-trans-decadienoyl-CoA to a Δ3- enoyl-CoA but not to a Δ2-enoyl-CoA. Kinetic analyses demonstrated that PDCR is active on a broad range of Δ24-dienoyl-CoAs. Although the observed substrate preference was to Δ2-trans,Δ4-trans-decadienoyl-CoA, PDCR was also active on a C22 substrate with multiple unsaturations, a result consistent with the role of peroxisomes in the oxidation of complex, very long chain, polyunsaturated fatty acids. The presence of a type-1 peroxisomal targeting signal Ala-Lys-Leu-COOH at the C terminus of PDCR suggested that this protein may be peroxisomal. We observed that tagged PDCR was efficiently transported to the peroxisome lumen in normal human fibroblasts but not in cells derived from a Zellweger syndrome patient with a specific defect in peroxisomal matrix protein import. We conclude that this protein resides within the peroxisome matrix and therefore represents the first mammalian peroxisomal Δ24-dienoyl-CoA reductase to be characterized at the molecular level.

Original languageEnglish (US)
Pages (from-to)25814-25820
Number of pages7
JournalJournal of Biological Chemistry
Volume274
Issue number36
DOIs
StatePublished - Sep 3 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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