6l3x - Revision history

OCA at 10:51, 22 November 2023

OCA — Wed, 22 Nov 2023 10:51:06 GMT

←Older revision		Revision as of 10:51, 22 November 2023
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	==Discovery of novel peptidomimetic boronate ClpP inhibitors with noncanonical enzyme mechanism as potent virulence blockers in vitro and in vivo==		==Discovery of novel peptidomimetic boronate ClpP inhibitors with noncanonical enzyme mechanism as potent virulence blockers in vitro and in vivo==
-	<StructureSection load='6l3x' size='340' side='right'caption='[[6l3x]]' scene=''>	+	<StructureSection load='6l3x' size='340' side='right'caption='[[6l3x]], [[Resolution\|resolution]] 2.31Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6L3X OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6L3X FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6l3x]] is a 14 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus_RF122 Staphylococcus aureus RF122]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6L3X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6L3X FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6l3x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l3x OCA], [~~http~~://pdbe.org/6l3x PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6l3x RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6l3x PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6l3x 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]] 2.3054Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=E4U:[(1~{R})-1-[[(2~{S})-2-[[2,5-bis(chloranyl)phenyl]carbonylamino]-3-(1~{H}-indol-3-yl)propanoyl]amino]-3-methyl-butyl]boronic+acid'>E4U</scene></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=6l3x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l3x OCA], [https://pdbe.org/6l3x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6l3x RCSB], [https://www.ebi.ac.uk/pdbsum/6l3x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6l3x ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/CLPP_STAAB CLPP_STAAB] Cleaves peptides in various proteins in a process that requires ATP hydrolysis. Has a chymotrypsin-like activity. Plays a major role in the degradation of misfolded proteins.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Caseinolytic protease P (ClpP) is considered as a promising target for the treatment of Staphylococcus aureus infections. In an unbiased screen of 2632 molecules, a peptidomimetic boronate, MLN9708, was found to be a potent suppressor of SaClpP function. A time-saving and cost-efficient strategy integrating in silico position scanning, multistep miniaturized synthesis, and bioactivity testing was deployed for optimization of this hit compound and led to fast exploration of structure-activity relationships. Five of 150 compounds from the miniaturized synthesis exhibited improved inhibitory activity. Compound 43Hf was the most active inhibitor and showed reversible covalent binding to SaClpP while did not destabilize the tetradecameric structure of SaClpP. The crystal structure of 43Hf-SaClpP complex provided mechanistic insight into the covalent binding mode of peptidomimetic boronate and SaClpP. Furthermore, 43Hf could bind endogenous ClpP in S. aureus cells and exhibited significant efficacy in attenuating S. aureus virulence in vitro and in vivo.
		+
		+	Discovery of Novel Peptidomimetic Boronate ClpP Inhibitors with Noncanonical Enzyme Mechanism as Potent Virulence Blockers in Vitro and in Vivo.,Ju Y, He L, Zhou Y, Yang T, Sun K, Song R, Yang Y, Li C, Sang Z, Bao R, Luo Y J Med Chem. 2020 Mar 26;63(6):3104-3119. doi: 10.1021/acs.jmedchem.9b01746. Epub , 2020 Feb 20. PMID:32031798<ref>PMID:32031798</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6l3x" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
		+	[[Category: Staphylococcus aureus RF122]]
	[[Category: Bao R]]		[[Category: Bao R]]
	[[Category: He LH]]		[[Category: He LH]]
	[[Category: Ju Y]]		[[Category: Ju Y]]
	[[Category: Luo YF]]		[[Category: Luo YF]]

OCA at 11:11, 26 August 2020

OCA — Wed, 26 Aug 2020 11:11:29 GMT

←Older revision		Revision as of 11:11, 26 August 2020
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-	'''Unreleased structure'''

-	~~The entry~~ 6l3x ~~is ON HOLD~~	+	==Discovery of novel peptidomimetic boronate ClpP inhibitors with noncanonical enzyme mechanism as potent virulence blockers in vitro and in vivo==
-		+	<StructureSection load='6l3x' size='340' side='right'caption='[[6l3x]]' scene=''>
-	~~Authors~~: ~~Luo~~, Y.F., ~~Bao~~, R., ~~Ju, Y~~., ~~He, L~~.H.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6L3X OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6L3X FirstGlance]. <br>
-	~~Description: Discovery of reversible covalent SaClpP inhibitors as potent anti-virulence agents by position ranking, sub-milligram scale synthesis and in situ biological assay~~	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6l3x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l3x OCA], [http://pdbe.org/6l3x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6l3x RCSB], [http://www.ebi.ac.uk/pdbsum/6l3x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6l3x ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Ju, Y~~]]	+	__TOC__
-	[[Category: He~~, L.H~~]]	+	</StructureSection>
-	[[Category: ~~Luo,~~ Y.F]]	+	[[Category: Large Structures]]
-	[[Category: ~~Bao, R~~]]	+	[[Category: Bao R]]
		+	[[Category: He LH]]
		+	[[Category: Ju Y]]
		+	[[Category: Luo YF]]

OCA: Protected "6l3x" [edit=sysop:move=sysop]

OCA — Wed, 23 Oct 2019 04:51:03 GMT

Protected "6l3x" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:51, 23 October 2019

OCA: New page: '''Unreleased structure''' The entry 6l3x is ON HOLD Authors: Luo, Y.F., Bao, R., Ju, Y., He, L.H. Description: Discovery of reversible covalent SaClpP inhibitors as potent anti-virule...

OCA — Wed, 23 Oct 2019 04:51:01 GMT

New page: '''Unreleased structure''' The entry 6l3x is ON HOLD Authors: Luo, Y.F., Bao, R., Ju, Y., He, L.H. Description: Discovery of reversible covalent SaClpP inhibitors as potent anti-virule...

New page

'''Unreleased structure'''

The entry 6l3x is ON HOLD

Authors: Luo, Y.F., Bao, R., Ju, Y., He, L.H.

Description: Discovery of reversible covalent SaClpP inhibitors as potent anti-virulence agents by position ranking, sub-milligram scale synthesis and in situ biological assay
[[Category: Unreleased Structures]]
[[Category: Ju, Y]]
[[Category: He, L.H]]
[[Category: Luo, Y.F]]
[[Category: Bao, R]]