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- Title
Crystal structures of homoserine dehydrogenase suggest a novel catalytic mechanism for oxidoreductases.
- Authors
DeLaBarre, Byron; Thompson, Paul R.; Wright, Gerard D.; Berghuis, Albert M.
- Abstract
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.
- Subjects
HYDROGENASE; SACCHAROMYCES cerevisiae; MICROSTRUCTURE
- Publication
Nature Structural Biology, 2000, Vol 7, Issue 3, p238
- ISSN
1072-8368
- Publication type
Article