1. Structure of pteridine reductase (PTR1) fromLeishmania tarentolae
- Author
-
Ming Zhao, Haiyan Zhao, David A. Matthews, Kottayil I. Varughese, Rose Ann Ferre, Tom Bray, John M. Whiteley, and Marc Ouellette
- Subjects
Models, Molecular ,Protein Conformation ,Stereochemistry ,Protozoan Proteins ,Crystal structure ,Crystallography, X-Ray ,Tetramer ,Structural Biology ,Oxidoreductase ,Animals ,Molecule ,Amino Acid Sequence ,Leishmania ,chemistry.chemical_classification ,biology ,Active site ,General Medicine ,biology.organism_classification ,Pteridine reductase ,Crystallography ,Enzyme ,chemistry ,biology.protein ,Oxidoreductases ,Sequence Alignment ,NADP - Abstract
The protozoan parasites Leishmania utilize a pteridine-reducing enzyme, pteridine reductase (PTR1), to bypass antifolate inhibition. The crystal structure of PTR1 from L. tarentolae has been solved as a binary complex with NADPH at 2.8 A resolution. The structure was solved by molecular-replacement techniques using the recently reported L. major PTR1 structure as a search model. Comparisons of the present structure with the L. major PTR1 allowed us to identify regions of flexibility in the molecule. PTR1 is a member of the growing family of short-chain dehydrogenases (SDR) which share the characteristic Tyr(Xaa)(3)Lys motif in the vicinity of the active site. The functional enzyme is a tetramer and the crystallographic asymmetric unit contains a tetramer with 222 point-group symmetry.
- Published
- 2003
- Full Text
- View/download PDF