TITLE

Crystal structure of Leishmania tarentolae hypoxanthine-guanine phosphoribosyltransferase

AUTHOR(S)
Monzani, Paulo S.; Trapani, Stefano; Thiemann, Otavio H.; Oliva, Glaucius
PUB. DATE
January 2007
SOURCE
BMC Structural Biology;2007, Vol. 7, p59
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) (EC 2.4.2.8) is a central enzyme in the purine recycling pathway. Parasitic protozoa of the order Kinetoplastida cannot synthesize purines de novo and use the salvage pathway to synthesize purine bases, making this an attractive target for antiparasitic drug design. Results: The glycosomal HGPRT from Leishmania tarentolae in a catalytically active form purified and co-crystallized with a guanosine monophosphate (GMP) in the active site. The dimeric structure of HGPRT has been solved by molecular replacement and refined against data extending to 2.1 Ã… resolution. The structure reveals the contacts of the active site residues with GMP. Conclusion: Comparative analysis of the active sites of Leishmania and human HGPRT revealed subtle differences in the position of the ligand and its interaction with the active site residues, which could be responsible for the different reactivities of the enzymes to allopurinol reported in the literature. The solution and analysis of the structure of Leishmania HGPRT may contribute to further investigations leading to a full understanding of this important enzyme family in protozoan parasites.
ACCESSION #
35111031

 

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