Open AccessStructure of Staphylococcus aureus cytidine monophosphate kinase in complex with cytidine 5′‐monophosphate
Author(s) -
Ren Jingshan,
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/s174430910602447x
Subject(s) - cytidine , staphylococcus aureus , active site , binding site , enzyme , transferase , escherichia coli , chemistry , biochemistry , stereochemistry , biology , gene , genetics , bacteria
The crystal structure of Staphylococcus aureus cytidine monophosphate kinase (CMK) in complex with cytidine 5′‐monophosphate (CMP) has been determined at 2.3 Å resolution. The active site reveals novel features when compared with two orthologues of known structure. Compared with the Streptococcus pneumoniae CMK solution structure of the enzyme alone, S. aureus CMK adopts a more closed conformation, with the NMP‐binding domain rotating by ∼16° towards the central pocket of the molecule, thereby assembling the active site. Comparing Escherichia coli and S. aureus CMK–CMP complex structures reveals differences within the active site, including a previously unreported indirect interaction of CMP with Asp33, the replacement of a serine residue involved in the binding of CDP by Ala12 in S. aureus CMK and an additional sulfate ion in the E. coli CMK active site. The detailed understanding of the stereochemistry of CMP binding to CMK will assist in the design of novel inhibitors of the enzyme. Inhibitors are required to treat the widespread hospital infection methicillin‐resistant S. aureus (MRSA), currently a major public health concern.