Open AccessStructure of Staphylococcus aureus guanylate monophosphate kinase
Author(s) -
El Omari Kamel,
Dhaliwal Balvinder,
Lockyer Michael,
Charles Ian,
Hawkins Alastair R.,
Stammers David K.
Publication year - 2006
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
ISSN - 1744-3091
DOI - 10.1107/s174430910603613x
Subject(s) - chemistry , dimer , guanylate kinase , stereochemistry , kinase , nucleotide , binding site , transferase , crystallography , biochemistry , enzyme , membrane protein , organic chemistry , membrane , gene
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.