Purification and preliminary characterization of four Rel homologues from pathogenic bacteria: Implications for species-specific inhibitor design.

Vinayak, Hegde and Apoorva, S. Raman and Pratik, Rajendra Patil and Balaji, Prakash (2021) Purification and preliminary characterization of four Rel homologues from pathogenic bacteria: Implications for species-specific inhibitor design. Protein Expression and Purification, 177. p. 105760. ISSN 1046-5928

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Abstract

Resistance to antibiotics is a serious concern to treat infectious diseases and also, for food preservation. Existing antibiotics generally inhibit enzymes participating in key bacterial processes, such as formation of cell wall, replication, transcription and translation. However, bacteria have rapidly evolved new mechanisms to combat these antibiotics and it hence becomes indispensable to identify newer targets and identify/design inhibitors against them. Another concern is that most antibiotics are broad spectrum; they largely bind and inhibit the active site of the target enzyme. Rel proteins, which synthesize (and hydrolyze) (p)ppGpp in response to a variety of stress encountered by bacteria, is a profitable target owing to its distinct absence in humans and an intricate regulation of the catalytic activities. Inactivation of (p)ppGpp synthesis by Rel, disables bacterial survival in Mycobacterium tuberculosis and Staphylococcus aureus, while inactivating the hydrolysis activity was lethal. The poor MIC values of the currently known Rel inhibitors present a distinct opportunity to develop better inhibitors and warrants a detailed structural characterization and understanding of the complex regulation in Rel proteins. It will open new avenues for the design of effective, species-specific inhibitors. In an attempt to identify unique sites for inhibitor design using structure-based approaches, we initiate a study of Rel homologues from four different pathogenic bacteria, in order to compare their attributes with well characterized Rel homologues. Here, we present cloning, over-expression, purification and preliminary characterization of these four homologues; and suggest similarities and differences that can be exploited for inhibitor design.

Item Type:	Article
Uncontrolled Keywords:	Rel homologues, pathogenic bacteria, pathogenic bacteria
Subjects:	600 Technology > 08 Food technology > 10 Food Microorganisms 600 Technology > 08 Food technology > 16 Nutritive value > 03 Proteins
Divisions:	Molecular Nutrition
Depositing User:	Food Sci. & Technol. Information Services
Date Deposited:	19 May 2023 11:25
Last Modified:	19 May 2023 11:25
URI:	http://ir.cftri.res.in/id/eprint/16432

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