Binary structure of the two-domain (3R)-hydroxyacyl-CoA dehydrogenase from rat peroxisomal multifunctional enzyme type 2 at 2.38 A resolution

Structure. 2003 Jan;11(1):87-97. doi: 10.1016/s0969-2126(02)00931-0.

Abstract

The crystal structure of (3R)-hydroxyacyl-CoA dehydrogenase of rat peroxisomal multifunctional enzyme type 2 (MFE-2) was solved at 2.38 A resolution. The catalytic entity reveals an alpha/beta short chain alcohol dehydrogenase/reductase (SDR) fold and the conformation of the bound nicotinamide adenine dinucleotide (NAD(+)) found in other SDR enzymes. Of great interest is the separate COOH-terminal domain, which is not seen in other SDR structures. This domain completes the active site cavity of the neighboring monomer and extends dimeric interactions. Peroxisomal diseases that arise because of point mutations in the dehydrogenase-coding region of the MFE-2 gene can be mapped to changes in amino acids involved in NAD(+) binding and protein dimerization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxyacyl CoA Dehydrogenases / chemistry*
  • 3-Hydroxyacyl CoA Dehydrogenases / genetics
  • 3-Hydroxyacyl CoA Dehydrogenases / metabolism
  • Amino Acid Sequence
  • Animals
  • Crystallography, X-Ray
  • Dimerization
  • Enoyl-CoA Hydratase / chemistry*
  • Enoyl-CoA Hydratase / genetics
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Multienzyme Complexes / chemistry*
  • Multienzyme Complexes / genetics
  • Peroxisomes / enzymology*
  • Protein Structure, Quaternary*
  • Rats
  • Rats, Wistar
  • Sequence Alignment

Substances

  • Multienzyme Complexes
  • 3-Hydroxyacyl CoA Dehydrogenases
  • Enoyl-CoA Hydratase

Associated data

  • PDB/1GZ6
  • PDB/R1GZ6SF