Crystal structures of homoserine dehydrogenase suggest a novel catalytic mechanism for oxidoreductases.
The structure of the antifungal drug target homoserine dehydrogenase (HSD) was determined from Saccharomyces cerevisiae in apo and holo forms, and as a ternary complex with bound products, by X-ray diffraction. The three forms show that the enzyme is a dimer, with each monomer composed of three regions, the nucleotide-binding ... region, the dimerization region and the catalytic region. The dimerization and catalytic regions have novel folds, whereas the fold of the nucleotide-binding region is a variation on the Rossmann fold. The novel folds impose a novel composition and arrangement of active site residues when compared to all other currently known oxidoreductases. This observation, in conjunction with site-directed mutagenesis of active site residues and steady-state kinetic measurements, suggest that HSD exhibits a new variation on dehydrogenase chemistry.
Mesh Terms:
Apoenzymes, Binding Sites, Catalysis, Catalytic Domain, Cations, Crystallography, X-Ray, Dimerization, Holoenzymes, Homoserine, Homoserine Dehydrogenase, Hydrogen, Metals, Models, Chemical, Models, Molecular, Molecular Sequence Data, Mutation, NAD, Protein Conformation, Protein Folding, Saccharomyces cerevisiae, Structure-Activity Relationship
Apoenzymes, Binding Sites, Catalysis, Catalytic Domain, Cations, Crystallography, X-Ray, Dimerization, Holoenzymes, Homoserine, Homoserine Dehydrogenase, Hydrogen, Metals, Models, Chemical, Models, Molecular, Molecular Sequence Data, Mutation, NAD, Protein Conformation, Protein Folding, Saccharomyces cerevisiae, Structure-Activity Relationship
Nat. Struct. Biol.
Date: Mar. 01, 2000
PubMed ID: 10700284
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