The First Structure of an Aldehyde Dehydrogenase Reveals Novel Interactions Between NAD and the Rossmann Fold

Nat Struct Biol. 1997 Apr;4(4):317-26. doi: 10.1038/nsb0497-317.

Abstract

The first structure of an aldehyde dehydrogenase (ALDH) is described at 2.6 A resolution. Each subunit of the dimeric enzyme contains an NAD-binding domain, a catalytic domain and a bridging domain. At the interface of these domains is a 15 A long funnel-shaped passage with a 6 x 12 A opening leading to a putative catalytic pocket. A new mode of NAD binding, which differs substantially from the classic beta-alpha-beta binding mode associated with the 'Rossmann fold', is observed which we term the beta-alpha,beta mode. Sequence comparisons of the class 3 ALDH with other ALDHs indicate a similar polypeptide fold, novel NAD-binding mode and catalytic site for this family. A mechanism for enzymatic specificity and activity is postulated.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aldehyde Dehydrogenase / chemistry*
  • Amino Acid Sequence
  • Binding Sites
  • Computer Simulation
  • Crystallography, X-Ray
  • Dimerization
  • Hydrogen Bonding
  • Models, Molecular
  • Molecular Sequence Data
  • NAD / chemistry*
  • Protein Conformation
  • Protein Folding
  • Sequence Homology, Amino Acid
  • Substrate Specificity

Substances

  • NAD
  • Aldehyde Dehydrogenase