Article
- The EMBO Journal (2004) 23, 1234 - 1244
- doi:10.1038/sj.emboj.7600147
Published online: 11 March 2004
Subject Categories:
Methanoarchaeal sulfolactate dehydrogenase: prototype of a new family of NADH-dependent enzymes
Adriana Irimia1,a, Dominique Madern1,a, Giuseppe Zaccaï1,2 and Frédéric MD Vellieux1
- Laboratoire de Biophysique Moléculaire, Institut de Biologie Structurale J-P Ebel CEA CNRS UJF, Grenoble, France
- Institut Laue Langevin, Grenoble, France
Correspondence to:
Frédéric MD Vellieux, Laboratoire de Biophysique Moléculaire, Institut de Biologie Structurale J-P Ebel CEA CNRS UJF, UMR-5075, 41 rue Jules Horowitz, 38027 Grenoble Cedex 01, France. Tel.: +33 438 789 605; Fax: +33 438 785 494; E-mail: vellieux@ibs.fr
aThese authors contributed equally to this work
Received 19 November 2003; Accepted 6 February 2004
Abstract
The crystal structure of the sulfolactate dehydrogenase from the hyperthermophilic and methanogenic archaeon Methanocaldococcus jannaschii was solved at 2.5 Å resolution (PDB id. 1RFM). The asymmetric unit contains a tetramer of tight dimers. This structure, complexed with NADH, does not contain a cofactor-binding domain with 'Rossmann-fold' topology. Instead, the tertiary and quaternary structures indicate a novel fold. The NADH is bound in an extended conformation in each active site, in a manner that explains the pro-S specificity. Cofactor binding involves residues belonging to both subunits within the tight dimers, which are therefore the smallest enzymatically active units. The protein was found to be a homodimer in solution by size-exclusion chromatography, analytical ultracentrifugation and small-angle neutron scattering. Various compounds were tested as putative substrates. The results indicate the existence of a substrate discrimination mechanism, which involves electrostatic interactions. Based on sequence homology and phylogenetic analyses, several other enzymes were classified as belonging to this novel family of homologous (S)-2-hydroxyacid dehydrogenases.
Keywords:
- coenzyme M,
- dehydrogenase,
- hyperthermostable,
- methanogens,
- pro-S hydrogen transfer
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