1q3t

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Revision as of 22:14, 20 November 2007


1q3t

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Solution structure and function of an essential CMP kinase of Streptococcus pneumoniae

Overview

Streptococcus pneumoniae is a major human pathogen that causes high, mortality and morbidity and has developed resistance to many antibiotics., We show that the gene product from SP1603, identified from S. pneumoniae, TIGR4, is a CMP kinase that is essential for bacterial growth. It, represents an attractive drug target for the development of a novel, antibiotic to overcome the problems of drug resistance development for, this organism. Here we describe the three-dimensional solution structure, of the S. pneumoniae CMP kinase as determined by NMR spectroscopy. The, structure consists of eight alpha-helices and two beta-sheets that fold, into the classical core domain, the substrate-binding domain, and the LID, domain. The three domains of the protein pack together to form a central, cavity for substrate-binding and enzymatic catalysis. The S. pneumoniae, CMP kinase resembles the fold of the Escherichia coli homolog. An, insertion of one residue is observed at the beta-turn in the, substrate-binding domain of the S. pneumoniae CMP kinase when compared, with the E. coli homolog. Chemical shift perturbations caused by the, binding of CMP, CDP, and ATP revealed that CMP or CDP binds to the, junction between the core and substrate-binding domains, whereas ATP binds, to the junction between the core and LID domains. From NMR relaxation, studies, we determined that the loops in the LID domain are highly mobile., These mobile loops could aid in the closing/opening of the LID domain, during enzyme catalysis.

About this Structure

1Q3T is a Single protein structure of sequence from Streptococcus pneumoniae. Active as Cytidylate kinase, with EC number 2.7.4.14 Full crystallographic information is available from OCA.

Reference

Solution structure and function of an essential CMP kinase of Streptococcus pneumoniae., Yu L, Mack J, Hajduk PJ, Kakavas SJ, Saiki AY, Lerner CG, Olejniczak ET, Protein Sci. 2003 Nov;12(11):2613-21. PMID:14573872

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