title: Structure of pteridine reductase (PTR1) from Leishmania tarentolae.
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.
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhao
authors.forename: Tom
authors.initials: T
authors.lastname: Bray
authors.forename: Marc
authors.initials: M
authors.lastname: Ouellette
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Rose Ann
authors.initials: RA
authors.lastname: Ferre
authors.forename: David
authors.initials: D
authors.lastname: Matthews
authors.forename: John M
authors.initials: JM
authors.lastname: Whiteley
authors.forename: Kottayil I
authors.initials: KI
authors.lastname: Varughese
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D007891:Leishmania / Q000201:enzymology*; D008958:Models, Molecular; D009249:NADP / Q000737:chemistry; D010088:Oxidoreductases / Q000737:chemistry* / Q000302:isolation & purification; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000737:chemistry; D016415:Sequence Alignment
chemical_list: D015800:Protozoan Proteins; D009249:NADP; D010088:Oxidoreductases; C085592:pteridine reductase