6gjm - Revision history

OCA at 08:42, 21 February 2019

OCA — Thu, 21 Feb 2019 08:42:14 GMT

←Older revision		Revision as of 08:42, 21 February 2019
Line 3:		Line 3:
	<StructureSection load='6gjm' size='340' side='right' caption='[[6gjm]], [[Resolution\|resolution]] 1.35Å' scene=''>		<StructureSection load='6gjm' size='340' side='right' caption='[[6gjm]], [[Resolution\|resolution]] 1.35Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6gjm]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GJM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GJM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6gjm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GJM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GJM FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=L36:ethyl+2-[[(4-aminophenyl)methyl-propyl-carbamoyl]amino]ethanoate'>L36</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=L36:ethyl+2-[[(4-aminophenyl)methyl-propyl-carbamoyl]amino]ethanoate'>L36</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PPIA, CYPA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8] </span></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6gjm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gjm OCA], [http://pdbe.org/6gjm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gjm RCSB], [http://www.ebi.ac.uk/pdbsum/6gjm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gjm ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6gjm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gjm OCA], [http://pdbe.org/6gjm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gjm RCSB], [http://www.ebi.ac.uk/pdbsum/6gjm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gjm ProSAT]</span></td></tr>
Line 10:		Line 11:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/PPIA_HUMAN PPIA_HUMAN]] PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.		[[http://www.uniprot.org/uniprot/PPIA_HUMAN PPIA_HUMAN]] PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Cyclophilins (Cyps) are a major family of drug targets that are challenging to prosecute with small molecules because the shallow nature and high degree of conservation of the active site across human isoforms offers limited opportunities for potent and selective inhibition. Herein a computational approach based on molecular dynamics simulations and free energy calculations was combined with biophysical assays and X-ray crystallography to explore a flip in the binding mode of a reported urea-based Cyp inhibitor. This approach enabled access to a distal pocket that is poorly conserved among key Cyp isoforms, and led to the discovery of a new family of sub-micromolar cell-active inhibitors that offer unprecedented opportunities for the development of next-generation drug therapies based on Cyp inhibition. The computational approach is applicable to a broad range of organic functional groups and could prove widely enabling in molecular design.
		+
		+	A computationally designed binding mode flip leads to a novel class of potent tri-vector cyclophilin inhibitors.,De Simone A, Georgiou C, Ioannidis H, Gupta AA, Juarez-Jimenez J, Doughty-Shenton D, Blackburn EA, Wear MA, Richards JP, Barlow PN, Carragher N, Walkinshaw MD, Hulme AN, Michel J Chem Sci. 2018 Oct 23;10(2):542-547. doi: 10.1039/c8sc03831g. eCollection 2019, Jan 14. PMID:30746096<ref>PMID:30746096</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6gjm" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Peptidylprolyl isomerase]]		[[Category: Peptidylprolyl isomerase]]
	[[Category: Georgiou, C]]		[[Category: Georgiou, C]]

OCA at 12:18, 7 November 2018

OCA — Wed, 07 Nov 2018 12:18:32 GMT

←Older revision		Revision as of 12:18, 7 November 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6gjm is ~~ON HOLD until Paper Publication~~	+	==Cyclophilin A complexed with tri-vector ligand 4.==
-		+	<StructureSection load='6gjm' size='340' side='right' caption='[[6gjm]], [[Resolution\|resolution]] 1.35Å' scene=''>
-	~~Authors~~: ~~Georgiou~~, C., ~~De Simone~~, A., ~~Walkinshaw~~, M.D., ~~Michel, J~~.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6gjm]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GJM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GJM FirstGlance]. <br>
-	~~Description~~: ~~Cyclophilin A complexed with tri~~-~~vector ligand 4~~.	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=L36:ethyl+2-[[(4-aminophenyl)methyl-propyl-carbamoyl]amino]ethanoate'>L36</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8] </span></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6gjm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gjm OCA], [http://pdbe.org/6gjm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gjm RCSB], [http://www.ebi.ac.uk/pdbsum/6gjm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gjm ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PPIA_HUMAN PPIA_HUMAN]] PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Peptidylprolyl isomerase]]
	[[Category: Georgiou, C]]		[[Category: Georgiou, C]]
	[[Category: Michel, J]]		[[Category: Michel, J]]
-	[[Category: De Simone, A]]	+	[[Category: Simone, A De]]
-	[[Category: Walkinshaw, M.D]]	+	[[Category: Walkinshaw, M D]]
		+	[[Category: Complex]]
		+	[[Category: Cyclophilin]]
		+	[[Category: Cypa]]
		+	[[Category: Inhibitor]]
		+	[[Category: Isomerase]]
		+	[[Category: Ppiase]]

OCA at 05:50, 14 June 2018

OCA — Thu, 14 Jun 2018 05:50:19 GMT

←Older revision		Revision as of 05:50, 14 June 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Georgiou, C., De Simone, A., Walkinshaw, M.D., Michel, J.		Authors: Georgiou, C., De Simone, A., Walkinshaw, M.D., Michel, J.

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

OCA — Wed, 23 May 2018 06:12:19 GMT

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

←Older revision

Revision as of 06:12, 23 May 2018

OCA: New page: '''Unreleased structure''' The entry 6gjm is ON HOLD Authors: Georgiou, C., De Simone, A., Walkinshaw, M.D., Michel, J. Description: Cyclophilin A complexed with tri-vector ligand 4. [...

OCA — Wed, 23 May 2018 06:12:17 GMT

New page: '''Unreleased structure''' The entry 6gjm is ON HOLD Authors: Georgiou, C., De Simone, A., Walkinshaw, M.D., Michel, J. Description: Cyclophilin A complexed with tri-vector ligand 4. [...

New page

'''Unreleased structure'''

The entry 6gjm is ON HOLD

Authors: Georgiou, C., De Simone, A., Walkinshaw, M.D., Michel, J.

Description: Cyclophilin A complexed with tri-vector ligand 4.
[[Category: Unreleased Structures]]
[[Category: Georgiou, C]]
[[Category: Michel, J]]
[[Category: De Simone, A]]
[[Category: Walkinshaw, M.D]]