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Computational studies on histidine kinase protein BaeS to target multidrug-resistant Salmonella

Sivakumar, Dakshinamurthy and Lahiri, Chandrajit and Chakravortty, Dipshikha (2013) Computational studies on histidine kinase protein BaeS to target multidrug-resistant Salmonella. In: MEDICINAL CHEMISTRY RESEARCH, 22 (4). pp. 1804-1811.

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Official URL: http://dx.doi.org/10.1007/s00044-012-0188-6

Abstract

Multidrug-resistant Salmonella serovars have been a recent concern in curing infectious diseases like typhoid. Salmonella BaeS and BaeR are the two-component system (TCS) that signal transduction proteins found to play an important role in its multidrug resistance. A canonical TCS comprises a histidine kinase (HK) and its cognate partner response regulator (RR). The general approaches for therapeutic targeting are either the catalytic ATP-binding domain or the dimerization domain HisKA (DHp) of the HK, and in some cases, the receiver or the regulatory domain of the RR proteins. Earlier efforts of identifying novel drugs targeting the signal transduction protein have not been quite successful, as it shares similar ATP-binding domain with the key house keeping gene products of the mammalian GHL family. However, targeting the dimerization domain of HisKA through which the signals are received from the RR can be a better approach. In this article, we show stepwise procedure to specifically identify the key interacting residues involved in the dimerization with the RR along with effective targeting by ligands screened from the public database. We have found a few inhibitors which target effectively the important residues for the dimerization activity. Our results suggest a plausible de novo design of better DHp domain inhibitors.

Item Type: Journal Article
Additional Information: Copyright for this article belongs to SPRINGER BIRKHAUSER, NEW YORK, USA
Keywords: Multidrug resistance;Salmonella;BaeS-R;Docking;XR770
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Depositing User: Francis Jayakanth
Date Deposited: 22 Mar 2013 07:28
Last Modified: 22 Mar 2013 07:28
URI: http://eprints.iisc.ac.in/id/eprint/46152

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