Title
Crystal structures of homoserine dehydrogenase suggest a novel catalytic mechanism for oxidoreductases
UMMS Affiliation
Department of Biochemistry and Molecular Pharmacology
Publication Date
2000-03-01
Document Type
Article
Subjects
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
Disciplines
Biochemistry | Enzymes and Coenzymes | Medicinal-Pharmaceutical Chemistry | Therapeutics
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.
DOI of Published Version
10.1038/73359
Source
Nat Struct Biol. 2000 Mar;7(3):238-44. Link to article on publisher's site
Journal/Book/Conference Title
Nature structural biology
Related Resources
Repository Citation
DeLaBarre B, Thompson PR, Wright GD, Berghuis AM. (2000). Crystal structures of homoserine dehydrogenase suggest a novel catalytic mechanism for oxidoreductases. Thompson Lab Publications. https://doi.org/10.1038/73359. Retrieved from https://escholarship.umassmed.edu/thompson/91
Comments
At the time of publication, Paul Thompson was not yet affiliated with UMass Medical School.