Harkiolaki, M., Dodson, E.J., Bernier-Villamor, V., Turkenburg, J.P., Gonzalez-Pacanowska, D. and Wilson, K.S. (2004) The crystal structure of Trypanosoma cruzi dUTPase reveals a novel dUTP/dUDP-binding fold. Structure, 12 (1). pp. 41-53. ISSN 0969-2126Full text not available from this repository.
dUTPase is an essential enzyme involved with nucleotide metabolism and replication. We report here the X-ray structure of Ttypanosoma 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 Angstrom 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.
|Academic Units:||The University of York > Chemistry (York)|
|Depositing User:||York RAE Import|
|Date Deposited:||10 Feb 2009 14:21|
|Last Modified:||10 Feb 2009 14:21|
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