Crystal structure of aldehyde dehydrogenase 1A1 from mouse

Biochem Biophys Res Commun. 2022 Nov 5:628:141-146. doi: 10.1016/j.bbrc.2022.08.054. Epub 2022 Sep 2.

Abstract

Aldehyde dehydrogenase 1A1 (ALDH1A1) is an enzyme that catalyzes the NAD+-dependent oxidation of aldehydes to carboxylic acids, participating in various metabolic processes. Currently, only structures from human and Ovis aries have been reported. Here we show a 2.89 Å resolution structure of ALDH1A1 from mice using X-ray crystallography. We performed a detailed analysis of the structure and compared it with ALDH1A1 structures from two other species, highlighting the significance of the differences. Structural superimposition reveals that the tetrameric molecule is asymmetrical, and the NAD+-binding domain exhibits a certain rotation. In addition, the noticeable structural differences were detected, including the unique contact between Ser461 and Asp148, as well as the side chain orientations of three amino acids residues, Asn474, Met471 and Phe466. This study helps to expand the structural diversity of the ALDH family.

Keywords: ALDH1A1; Aldehyde dehydrogenase; Oligomerization; X-ray crystallography.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde Dehydrogenase 1 Family* / chemistry
  • Aldehyde Dehydrogenase 1 Family* / metabolism
  • Aldehyde Dehydrogenase* / chemistry
  • Aldehyde Dehydrogenase* / metabolism
  • Aldehydes / metabolism
  • Amino Acids
  • Animals
  • Carboxylic Acids
  • Crystallography, X-Ray
  • Mice
  • NAD* / metabolism
  • Retinal Dehydrogenase* / chemistry
  • Retinal Dehydrogenase* / metabolism

Substances

  • Aldehydes
  • Amino Acids
  • Carboxylic Acids
  • NAD
  • Aldehyde Dehydrogenase 1 Family
  • Aldehyde Dehydrogenase
  • ALDH1A1 protein, mouse
  • Retinal Dehydrogenase