Crystal structure of the Escherichia coli dUTPase in complex with a substrate analogue (dUDP)
- 1 June 1996
- journal article
- Published by Springer Nature in Nature Structural & Molecular Biology
- Vol. 3 (6), 532-538
- https://doi.org/10.1038/nsb0696-532
Abstract
We have determined the structure of the homotrimeric dUTPase from Escherichia coli, completed with an inhibitor and substrate analogue, dUDP. Three molecules of dUDP are found symmetrically bound per trimer, each in a shallow cleft between adjacent subunits, interacting with evolutionary conserved residues. The interactions of the uracil ring and the deoxypentose with the protein are consistent with the high specificity of the enzyme with respect to these groups. The positions of the two phosphate groups and adjacent water molecules are discussed in relation to the mechanism and kinetics of catalysis. The role that dUTPase plays in DNA metabolism makes the enzyme a potential target for chemotherapeutic drugs: the results presented here will aid in the design and development of inhibitory compounds.Keywords
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