Sen, Himanshu and Choudhury, Gourab Basu and Pawar, Ganesh and Sharma, Yogesh and Bhalerao, Sonali Eknath and Chaudhari, Vinod D and Datta, Saumen and Raychaudhuri, Saumya (2023) Diversity in the ligand binding pocket of HapR attributes to its uniqueness towards several inhibitors with respect to other homologues - A structural and molecular perspective. Int. J. Biol. Macromol., 233 (123495). p. 123495.
Full text not available from this repository. (Request a copy)Abstract
Vibrio cholerae is a prolific bacterium. Cumulative studies clearly demonstrate the key role of quorum sensing on the lifecycle of this bacterium. Of the sensory network components, HapR is known as high cell density master regulator. Until now, no information is available on native HapR ligand despite the protein having a ligand binding pocket. Interestingly, function of SmcR, a HapR homologue of Vibrio vulnificus is inhibited by a small molecule Qstatin. Structural analysis of SmcR with Qstatin identifies key interacting residues in SmcR ligand binding domain. Despite bearing significant homology with SmcR, HapR function remained unabated by Qstatin. Sequence alignment indicates divergence in the key residues of ligand binding pocket between these two regulators. A series of ligand binding domain mutants of HapR was constructed where only HapR quadruple mutant responded to Qstatin and newly synthesized IMT-VC-212. Crystal structure analysis revealed four key residues are responsible for changes in the volume of ligand binding pocket of HapR quadruple mutant compared to the wild type counterpart, thereby increasing the accessibility of Qstatin and its derivative in case of the former. The mechanistic insights exuberating from this study will remain instrumental in designing inhibitors against wild type HapR.
| Item Type: | Article |
|---|---|
| Additional Information: | Copyright of this article belongs to Elsevier BV |
| Uncontrolled Keywords: | Crystal structure; Qstatin; Quorum sensing; SmcR; Vibrio cholerae |
| Subjects: | Q Science > QR Microbiology |
| Depositing User: | Dr. K.P.S.Sengar |
| Date Deposited: | 25 Mar 2026 05:06 |
| Last Modified: | 25 Mar 2026 05:06 |
| URI: | http://crdd.osdd.net/open/id/eprint/3390 |
Actions (login required)
 |
View Item |
