6xrp - Revision history

OCA at 14:59, 18 October 2023

2023-10-18T14:59:44Z

←Older revision		Revision as of 14:59, 18 October 2023
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-	====	+	==Crystal structure of GlpG in complex with peptide ketoamide inhibitor, Ac-RVWHA-ketoamide-phenylbutyl==
-	<StructureSection load='6xrp' size='340' side='right'caption='[[6xrp]]' scene=''>	+	<StructureSection load='6xrp' size='340' side='right'caption='[[6xrp]], [[Resolution\|resolution]] 2.40Å' 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= OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6xrp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster] and [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XRP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XRP 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=6xrp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xrp OCA], [~~http~~://pdbe.org/6xrp PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6xrp RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6xrp PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6xrp 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]] 2.4Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=V87:N-(4-phenylbutyl)formamide'>V87</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=6xrp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xrp OCA], [https://pdbe.org/6xrp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xrp RCSB], [https://www.ebi.ac.uk/pdbsum/6xrp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xrp ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/GLPG_ECOLI GLPG_ECOLI] Rhomboid-type serine protease that catalyzes intramembrane proteolysis.<ref>PMID:17099694</ref> <ref>PMID:16216077</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Rhomboid intramembrane proteases regulate pathophysiological processes, but their targeting in a disease context has never been achieved. We decoded the atypical substrate specificity of malaria rhomboid PfROM4, but found, unexpectedly, that it results from "steric exclusion": PfROM4 and canonical rhomboid proteases cannot cleave each other's substrates due to reciprocal juxtamembrane steric clashes. Instead, we engineered an optimal sequence that enhanced proteolysis >10-fold, and solved high-resolution structures to discover that boronates enhance inhibition >100-fold. A peptide boronate modeled on our "super-substrate" carrying one "steric-excluding" residue inhibited PfROM4 but not human rhomboid proteolysis. We further screened a library to discover an orthogonal alpha-ketoamide that potently inhibited PfROM4 but not human rhomboid proteolysis. Despite the membrane-immersed target and rapid invasion, ultrastructural analysis revealed that single-dosing blood-stage malaria cultures blocked host-cell invasion and cleared parasitemia. These observations establish a strategy for designing parasite-selective rhomboid inhibitors and expose a druggable dependence on rhomboid proteolysis in non-motile parasites.
		+
		+	Designed Parasite-Selective Rhomboid Inhibitors Block Invasion and Clear Blood-Stage Malaria.,Gandhi S, Baker RP, Cho S, Stanchev S, Strisovsky K, Urban S Cell Chem Biol. 2020 Aug 31. pii: S2451-9456(20)30333-0. doi:, 10.1016/j.chembiol.2020.08.011. PMID:32888502<ref>PMID:32888502</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6xrp" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Rhomboid protease\|Rhomboid protease]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Drosophila melanogaster]]
		+	[[Category: Escherichia coli]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Cho S]]
		+	[[Category: Urban S]]

OCA at 09:50, 16 September 2020

2020-09-16T09:50:09Z

←Older revision		Revision as of 09:50, 16 September 2020
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-	'''Unreleased structure'''

-	~~The entry~~ 6xrp ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='6xrp' size='340' side='right'caption='[[6xrp]]' scene=''>
-	~~Authors~~: ~~Urban, S~~.~~, Cho, S~~.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description~~: ~~Crystal structure of GlpG in complex with peptide ketoamide inhibitor~~, Ac-~~RVWHA-ketoamide-phenylbutyl~~	+	</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=6xrp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xrp OCA], [http://pdbe.org/6xrp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6xrp RCSB], [http://www.ebi.ac.uk/pdbsum/6xrp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6xrp ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[Category: ~~Urban, S~~]]	+	__TOC__
-	[[Category: ~~Cho, S~~]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 04:31, 19 August 2020

2020-08-19T04:31:44Z

←Older revision		Revision as of 04:31, 19 August 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6xrp is ON HOLD	+	The entry 6xrp is ON HOLD until Paper Publication

	Authors: Urban, S., Cho, S.		Authors: Urban, S., Cho, S.
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	Description: Crystal structure of GlpG in complex with peptide ketoamide inhibitor, Ac-RVWHA-ketoamide-phenylbutyl		Description: Crystal structure of GlpG in complex with peptide ketoamide inhibitor, Ac-RVWHA-ketoamide-phenylbutyl
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Cho, S]]
	[[Category: Urban, S]]		[[Category: Urban, S]]
		+	[[Category: Cho, S]]

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

2020-07-22T06:57:22Z

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

←Older revision

Revision as of 06:57, 22 July 2020

OCA: New page: '''Unreleased structure''' The entry 6xrp is ON HOLD Authors: Urban, S., Cho, S. Description: Crystal structure of GlpG in complex with peptide ketoamide inhibitor, Ac-RVWHA-ketoamide-...

2020-07-22T06:57:21Z

New page: '''Unreleased structure''' The entry 6xrp is ON HOLD Authors: Urban, S., Cho, S. Description: Crystal structure of GlpG in complex with peptide ketoamide inhibitor, Ac-RVWHA-ketoamide-...

New page

'''Unreleased structure'''

The entry 6xrp is ON HOLD

Authors: Urban, S., Cho, S.

Description: Crystal structure of GlpG in complex with peptide ketoamide inhibitor, Ac-RVWHA-ketoamide-phenylbutyl
[[Category: Unreleased Structures]]
[[Category: Cho, S]]
[[Category: Urban, S]]