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- Title
Searching for Potential Drug Targets in Two-component and Phosphorelay Signal-transduction Systems using Three-dimensional Cluster Analysis.
- Authors
Cai, Xiao-Hui; Zhang, Qing; Shi, Shuo-Yong; Ding, Da-Fu
- 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.Edited byYi-Fei WANG
- Subjects
CELLULAR signal transduction; DRUG target; TARGET organs (Anatomy); PHYSIOLOGICAL control systems; MICROBIAL virulence; PATHOGENIC microorganisms; DRUG resistance in microorganisms; PROTEIN-protein interactions
- Publication
Acta Biochimica et Biophysica Sinica, 2005, Vol 37, Issue 5, p293
- ISSN
1672-9145
- Publication type
Article
- DOI
10.1111/j.1745-7270.2005.00046.x