Crystal structure and active site location of N-(1-D-carboxylethyl)-L-norvaline dehydrogenase.

Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, The University of Sheffield, UK. kbritton@sheffield.ac.uk

Opine dehydrogenases catalyze the NAD(P)H-dependent reversible reaction to form opines that contain two asymmetric centers exhibiting either (L,L) or (D,L) stereochemistry. The first structure of a (D,L) superfamily member, N-(1-D-carboxylethyl)-L-norvaline dehydrogenase (CENDH) from Arthrobacter sp. strain 1C, has been determined at 1.8 A resolution and the location of the bound nucleotide coenzyme has been identified. Six conserved residues cluster in the cleft between the enzyme's two domains, close to the nucleotide binding site, and are presumed to define the enzyme's catalytic machinery. Conservation of a His-Asp pair as part of this cluster suggests that the enzyme mechanism is related to the 2-hydroxy acid dehydrogenases. The pattern of sequence conservation and substitution between members of this enzyme family has permitted the tentative location of the residues that define their differential substrate specificities.

PMID: 9665174 [PubMed - indexed for MEDLINE]