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ISSN
1672-9145
Acta Biochim Biophys Sin
2005, 37(5): 293–302
CN 31-1940/Q
Searching for Potential Drug Targets in Two-component and
Phosphorelay Signal-transduction Systems using Three-dimensional Cluster
Analysis
Xiao-Hui CAI#, Qing ZHANG#, Shuo-Yong SHI, and
Da-Fu DING*
Key Laboratory of Proteomics, Institute of Biochemistry and Cell
Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of
Sciences,
Graduate School of the Chinese Academy of Sciences, Shanghai 200031,
China
Abstract Two-component and
phosphorelay signal transduction systems are central components in the
virulence and antimicrobial resistance responses of a number of bacterial and
fungal pathogens; in some cases, these systems are essential for bacterial
growth and viability. Herein, we analyze in detail the conserved surface
residue clusters in the phosphotransferase domain of histidine kinases and the
regulatory domain of response regulators by using complex structure-based
three-dimensional cluster analysis. We also investigate the protein-protein
interactions that these residue clusters participate in. The Spo0B-Spo0F
complex structure was used as the reference structure, and the multiple
aligned sequences of phosphotransferases and response regulators were paired
correspondingly. The results show that a contiguous conserved residue cluster
is formed around the active site, which crosses the interface of histidine
kinases and response regulators. The conserved residue clusters of
phosphotransferase and the regulatory domains are directly involved in the
functional implementation of two-component signal transduction systems and are
good targets for the development of novel antimicrobial agents.
Key words two-component system;
phosphorelay; histidine kinase; response regulator; three-dimensional cluster
analysis
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Received: January 8, 2005 Accepted: March 7, 2005
This work was supported by the grants from the National High
Technology Research and Development Program of China (No. 2002AA234021) and the
Knowledge Innovation Program of the Chinese Academy of Sciences (KJCX1-08,
KSCX2-2-07)
#These authors contributed equally to
this work
*Corresponding author: Tel, 86-21-54921254; Fax, 86-21-54921011;
E-mail, [email protected]