A structural basis for substrate selectivity and stereoselectivity in octopine dehydrogenase from Pecten maximus

J Mol Biol. 2008 Aug 1;381(1):200-11. doi: 10.1016/j.jmb.2008.06.003. Epub 2008 Jun 7.


Octopine dehydrogenase [N(2)-(D-1-carboxyethyl)-L-arginine:NAD(+) oxidoreductase] (OcDH) from the adductor muscle of the great scallop Pecten maximus catalyzes the reductive condensation of l-arginine and pyruvate to octopine during escape swimming. This enzyme, which is a prototype of opine dehydrogenases (OpDHs), oxidizes glycolytically born NADH to NAD(+), thus sustaining anaerobic ATP provision during short periods of strenuous muscular activity. In contrast to some other OpDHs, OcDH uses only l-arginine as the amino acid substrate. Here, we report the crystal structures of OcDH in complex with NADH and the binary complexes NADH/l-arginine and NADH/pyruvate, providing detailed information about the principles of substrate recognition, ligand binding and the reaction mechanism. OcDH binds its substrates through a combination of electrostatic forces and size selection, which guarantees that OcDH catalysis proceeds with substrate selectivity and stereoselectivity, giving rise to a second chiral center and exploiting a "molecular ruler" mechanism.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Oxidoreductases / chemistry*
  • Amino Acid Oxidoreductases / genetics
  • Amino Acid Oxidoreductases / metabolism*
  • Amino Acid Sequence
  • Animals
  • Arginine / metabolism
  • Binding Sites
  • Catalysis
  • Crystallography, X-Ray
  • Kinetics
  • Models, Molecular
  • Molecular Sequence Data
  • NAD / chemistry
  • NAD / metabolism
  • Pecten / enzymology*
  • Pecten / genetics
  • Protein Binding
  • Protein Folding
  • Protein Structure, Tertiary
  • Pyruvic Acid / chemistry
  • Pyruvic Acid / metabolism
  • Sequence Alignment
  • Stereoisomerism
  • Substrate Specificity


  • NAD
  • Pyruvic Acid
  • Arginine
  • Amino Acid Oxidoreductases
  • D-octopine dehydrogenase