Publication Abstract from PubMed
The structure of Leishmania major pteridine reductase (PTR1) in complex with NADPH and the inhibitor 2,4,6-triaminoquinazoline (TAQ) has been solved in a new crystal form by molecular replacement and refined to 2.6 A resolution. The inhibitor mimics a fragment, the pterin head group, of the archetypal antifolate drug methotrexate (MTX) and exploits similar chemical features to bind in the PTR1 active site. Despite being a much smaller molecule, TAQ displays a similar inhibition constant to that of MTX. PTR1 is a target for the development of improved therapies for infections caused by trypanosomatid parasites and this analysis provides information to assist the structure-based development of novel enzyme inhibitors.
Inhibition of Leishmania major pteridine reductase by 2,4,6-triaminoquinazoline: structure of the NADPH ternary complex.,McLuskey K, Gibellini F, Carvalho P, Avery MA, Hunter WN Acta Crystallogr D Biol Crystallogr. 2004 Oct;60(Pt 10):1780-5. Epub 2004, Sep 23. PMID:15388924[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
