Crystal structures of homoserine dehydrogenase suggest a novel catalytic mechanism for oxidoreductases
UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyDocument Type
Journal ArticlePublication Date
2000-03-01Keywords
ApoenzymesBinding 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
Biochemistry
Enzymes and Coenzymes
Medicinal-Pharmaceutical Chemistry
Therapeutics
Metadata
Show full item recordAbstract
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.Source
Nat Struct Biol. 2000 Mar;7(3):238-44. Link to article on publisher's siteDOI
10.1038/73359Permanent Link to this Item
http://hdl.handle.net/20.500.14038/50087Notes
At the time of publication, Paul Thompson was not yet affiliated with UMass Medical School.
Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1038/73359