Publication Abstract from PubMed
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.
Crystal structures of homoserine dehydrogenase suggest a novel catalytic mechanism for oxidoreductases.,DeLaBarre B, Thompson PR, Wright GD, Berghuis AM Nat Struct Biol. 2000 Mar;7(3):238-44. PMID:10700284[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
