The crystal structure of Trypanosoma cruzi dUTPase reveals a novel dUTP/dUDP binding fold |
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Authors: | Harkiolaki Maria Dodson Eleanor J Bernier-Villamor Victor Turkenburg Johan P González-Pacanowska Dolores Wilson Keith S |
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Affiliation: | Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York YO10 5YW, UK. |
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Abstract: | 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. |
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