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Lookup NU author(s): Professor Alastair Hawkins
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Nucleotide monophosphate kinases (NMPKs) are potential antimicrobial drug targets owing to their role in supplying DNA and RNA precursors. The present work reports the crystal structure of Staphylococcus aureus guanylate monophosphate kinase (SaGMK) at 1.9 Å resolution. The structure shows that unlike most GMKs SaGMK is dimeric, confirming the role of the extended C-terminus in dimer formation as first observed for Escherichia coli GMK (EcGMK). One of the two SaGMK dimers within the crystal asymmetric unit has two monomers in different conformations: an open form with a bound sulfate ion (mimicking the β-phosphate of ATP) and a closed form with bound GMP and sulfate ion. GMP-induced domain movements in SaGMK can thus be defined by comparison of these conformational states. Like other GMKs, the binding of GMP firstly triggers a partial closure of the enzyme, diminishing the distance between the GMP-binding and ATP-binding sites. In addition, the closed structure shows the presence of a potassium ion in contact with the guanine ring of GMP. The potassium ion appears to form an integral part of the GMP-binding site, as the Tyr36 side chain has significantly moved to form a metal ion-ligand coordination involving the lone pair of the side-chain O atom. The potassium-binding site might also be exploited in the design of novel inhibitors. © International Union of Crystallography, 2006.
Author(s): El Omari K, Dhaliwal B, Lockyer M, Charles I, Hawkins AR, Stammers DK
Publication type: Article
Publication status: Published
Journal: Acta Crystallographica Section F: Structural Biology and Crystallization Communications
Year: 2006
Volume: 62
Issue: 10
Pages: 949-953
ISSN (electronic): 1744-3091
Publisher: Wiley-Blackwell
URL: http://dx.doi.org/10.1107/S174430910603613X
DOI: 10.1107/S174430910603613X
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