Searching for potential drug targets in two-component and phosphorelay signal-transduction systems using three-dimensional cluster analysis |
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Authors: | Cai Xiao-Hui Zhang Qing Shi Shuo-Yong Ding Da-Fu |
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Institution: | 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. |
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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. |
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Keywords: | two-component system phosphorelay histidine kinase response regulator three-dimensional cluster analysis |
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