1w2y: Difference between revisions

The crystal structure of the dUTPase from the important gastric pathogen, Campylobacter jejuni has been solved at 1.65 A spacing. This essential, bacterial enzyme is the second representative of the new family of dimeric, dUTPases to be structurally characterised. Members of this family have a, novel all-alpha fold and are unrelated to the all-beta dUTPases of the, majority of organisms including eukaryotes such as humans, bacteria such, as Escherichia coli, archaea like Methanococcus jannaschii and animal, viruses. Therefore, dimeric dUTPases can be considered as candidate drug, targets. The X-ray structure of the C.jejuni dUTPase in complex with the, non-hydrolysable substrate analogue dUpNHp allows us to define the, positions of three catalytically significant phosphate-binding magnesium, ions and provides a starting point for a detailed understanding of the, mechanism of dUTP/dUDP hydrolysis by dimeric dUTPases. Indeed, a water, molecule present in the structure is ideally situated to act as the, attacking nucleophile during hydrolysis. A comparison of the dUTPases from, C.jejuni and Trypanosoma cruzi reveals a common fold with certain distinct, features, both in the rigid and mobile domains as defined in the T.cruzi, structure. Homologues of the C.jejuni dUTPase have been identified in, several other bacteria and bacteriophages, including the dCTPase of phage, T4. Sequence comparisons of these proteins define a new superfamily of, d(C/U)TPases that includes three distinct enzyme families: (1) dUTPases in, trypanosomatides, C.jejuni and several other Gram-negative bacteria, (2), predicted dUTPases in various Gram-positive bacteria and their phages, and, (3) dCTP/dUTPases in enterobacterial T4-like phages. All these enzymes, share a basic module that consists of two alpha-helices from the rigid, domain, two helices from the mobile domain and connecting loops. These, results in concert with a number of conserved residues responsible for, interdomain cross-talk provide valuable insight towards rational drug, design.

1W2Y is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Campylobacter_jejuni Campylobacter jejuni] with MG and DUN as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/dUTP_diphosphatase dUTP diphosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.23 3.6.1.23] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1W2Y OCA].  

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