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The crystal structure of Staphylococcus aureus cytidine monophosphate kinase (CMK) in complex with cytidine 5'-monophosphate (CMP) has been determined at 2.3 angstroms 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 approximately 16 degrees 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.

Original publication

DOI

10.1107/S174430910602447X

Type

Journal article

Journal

Acta Crystallogr Sect F Struct Biol Cryst Commun

Publication Date

01/08/2006

Volume

62

Pages

710 - 715

Keywords

Amino Acid Sequence, Bacterial Proteins, Conserved Sequence, Crystallography, X-Ray, Cytidine Monophosphate, Models, Molecular, Molecular Sequence Data, Nucleoside-Phosphate Kinase, Protein Conformation, Sequence Homology, Amino Acid, Staphylococcus aureus