Candida tropicalis expresses two mitochondrial 2-enoyl thioester reductases that are able to form both homodimers and heterodimers

J Biol Chem. 2003 Oct 17;278(42):41213-20. doi: 10.1074/jbc.M307664200. Epub 2003 Jul 30.

Abstract

Here we report on the cloning of a Candida tropicalis gene, ETR2, that is closely related to ETR1. Both genes encode enzymatically active 2-enoyl thioester reductases involved in mitochondrial synthesis of fatty acids (fatty acid synthesis type II) and respiratory competence. The 5'- and 3'-flanking (coding) regions of ETR2 and ETR1 are about 90% (97%) identical, indicating that the genes have evolved via gene duplication. The gene products differ in three amino acid residues: Ile67 (Val), Ala92 (Thr), and Lys251 (Arg) in Etr2p (Etr1p). Quantitative PCR analysis and reverse transcriptase-PCR indicated that both genes were expressed about equally in fermenting and ETR1 predominantly respiring yeast cells. Like the situation with ETR1, expression of ETR2 in respiration-deficient Saccharomyces cerevisiae mutant cells devoid of Ybr026p/Etr1p was able to restore growth on glycerol. Triclosan that is used as an antibacterial agent against fatty acid synthesis type II 2-enoyl thioester reductases inhibited growth of FabI overexpressing mutant yeast cells but was not able to inhibit respiratory growth of the ETR2- or ETR1-complemented mutant yeast cells. Resolving of crystal structures obtained via Etr2p and Etr1p co-crystallization indicated that all possible dimer variants occur in the same asymmetric unit, suggesting that similar dimer formation also takes place in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Candida tropicalis / enzymology*
  • Crystallography, X-Ray
  • DNA Primers / chemistry
  • Dimerization
  • Enoyl-(Acyl-Carrier Protein) Reductase (NADPH, B-Specific)
  • Fermentation
  • Genetic Complementation Test
  • Glucose / metabolism
  • Mass Spectrometry
  • Mitochondria / enzymology*
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • NADH, NADPH Oxidoreductases / metabolism*
  • Oleic Acid / metabolism
  • Oxidoreductases Acting on CH-CH Group Donors
  • Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins

Substances

  • DNA Primers
  • Saccharomyces cerevisiae Proteins
  • Oleic Acid
  • Oxidoreductases Acting on CH-CH Group Donors
  • Enoyl-(Acyl-Carrier Protein) Reductase (NADPH, B-Specific)
  • Etr1 protein, S cerevisiae
  • trans-2-enoyl-CoA reductase (NADPH)
  • NADH, NADPH Oxidoreductases
  • Glucose

Associated data

  • GENBANK/U94996
  • PDB/1N96