7xxs
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7xxs]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Vibrio_cholerae Vibrio cholerae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7XXS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XXS FirstGlance]. <br> | <table><tr><td colspan='2'>[[7xxs]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Vibrio_cholerae Vibrio cholerae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7XXS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XXS FirstGlance]. <br> | ||
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7xxs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xxs OCA], [https://pdbe.org/7xxs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xxs RCSB], [https://www.ebi.ac.uk/pdbsum/7xxs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xxs ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.25Å</td></tr> |
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7xxs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xxs OCA], [https://pdbe.org/7xxs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xxs RCSB], [https://www.ebi.ac.uk/pdbsum/7xxs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xxs ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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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. | 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. | ||
| - | 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.,Sen H, Choudhury GB, Pawar G, Sharma Y, Bhalerao SE, Chaudhari VD, Datta S, Raychaudhuri S Int J Biol Macromol. 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.,Sen H, Choudhury GB, Pawar G, Sharma Y, Bhalerao SE, Chaudhari VD, Datta S, Raychaudhuri S Int J Biol Macromol. 2023 Apr 1;233:123495. doi: 10.1016/j.ijbiomac.2023.123495. , Epub 2023 Feb 2. PMID:36739058<ref>PMID:36739058</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
Current revision
HapR mutant I141V
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