Structural highlights
Function
[PTR1_LEITA] Exhibits a NADPH-dependent biopterin reductase activity. Has good activity with folate and significant activity with dihydrofolate and dihydrobiopterin, but not with quinonoid dihydrobiopterin. Confers resistance to methotrexate (MTX).
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Structure of pteridine reductase (PTR1) from Leishmania tarentolae.,Zhao H, Bray T, Ouellette M, Zhao M, Ferre RA, Matthews D, Whiteley JM, Varughese KI Acta Crystallogr D Biol Crystallogr. 2003 Sep;59(Pt 9):1539-44. Epub 2003, Aug 19. PMID:12925782[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zhao H, Bray T, Ouellette M, Zhao M, Ferre RA, Matthews D, Whiteley JM, Varughese KI. Structure of pteridine reductase (PTR1) from Leishmania tarentolae. Acta Crystallogr D Biol Crystallogr. 2003 Sep;59(Pt 9):1539-44. Epub 2003, Aug 19. PMID:12925782
