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Publication Abstract from PubMed

dUTPase is an essential enzyme involved with nucleotide metabolism and replication. We report here the X-ray structure of Trypanosoma cruzi dUTPase in its native conformation and as a complex with dUDP. These reveal a novel protein fold that displays no structural similarities to previously described dUTPases. The molecular unit is a dimer with two active sites. Nucleotide binding promotes extensive structural rearrangements, secondary structure remodeling, and rigid body displacements of 20 A or more, which effectively bury the substrate within the enzyme core for the purpose of hydrolysis. The molecular complex is a trapped enzyme-substrate arrangement which clearly demonstrates structure-induced specificity and catalytic potential. This enzyme is a novel dUTPase and therefore a potential drug target in the treatment of Chagas' disease.

The crystal structure of Trypanosoma cruzi dUTPase reveals a novel dUTP/dUDP binding fold.,Harkiolaki M, Dodson EJ, Bernier-Villamor V, Turkenburg JP, Gonzalez-Pacanowska D, Wilson KS Structure. 2004 Jan;12(1):41-53. PMID:14725764^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.