6x3y - Revision history

OCA at 14:41, 18 October 2023

OCA — Wed, 18 Oct 2023 14:41:43 GMT

←Older revision		Revision as of 14:41, 18 October 2023
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	<StructureSection load='6x3y' size='340' side='right'caption='[[6x3y]], [[Resolution\|resolution]] 1.40Å' scene=''>		<StructureSection load='6x3y' size='340' side='right'caption='[[6x3y]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6x3y]] 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=6X3Y OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6X3Y FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6x3y]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6X3Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6X3Y FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UMM:tert-butyl+[(2S)-1-{[(3S,17S)-2,16-dioxo-10,15-dioxa-1,21-diazatricyclo[15.3.1.1~5,9~]docosa-5(22),6,8-trien-3-yl]amino}-3-methyl-1-oxobutan-2-yl]carbamate'>UMM</scene~~></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]] 1.4Å</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UMM:tert-butyl+[(2S)-1-{[(3S,17S)-2,16-dioxo-10,15-dioxa-1,21-diazatricyclo[15.3.1.1~5,9~]docosa-5(22),6,8-trien-3-yl]amino}-3-methyl-1-oxobutan-2-yl]carbamate'>UMM</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=6x3y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6x3y OCA], [https://pdbe.org/6x3y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6x3y RCSB], [https://www.ebi.ac.uk/pdbsum/6x3y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6x3y ProSAT]</span></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=6x3y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6x3y OCA], [~~http~~://pdbe.org/6x3y PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6x3y RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6x3y PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6x3y ProSAT]</span></td></tr>	+
	</table>		</table>
	== 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.	+	[https://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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Peptidylprolyl isomerase]]~~	+	[[Category: Appleby TC]]
-	[[Category: Appleby~~, T C~~]]	+	[[Category: Paulsen JL]]
-	[[Category: Paulsen~~, J L~~]]	+	[[Category: Schmitz U]]
-	[[Category: Schmitz, U]]	+	[[Category: Shivakumar D]]
-	[[Category: Shivakumar, D]]	+
-	~~[[Category: Cyclophilin some]]~~	+
-	~~[[Category: Isomerase-isomerase inhibitor complex]]~~	+
-	~~[[Category: Macrocylcic inhibitor]]~~	+
-	~~[[Category: Peptidomimetic]]~~	+
-	~~[[Category: Prolyl isomerase]]~~	+
-	~~[[Category: Sanglifehrin some~~]]	+

OCA at 11:36, 26 August 2020

OCA — Wed, 26 Aug 2020 11:36:53 GMT

←Older revision		Revision as of 11:36, 26 August 2020
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	==Human cyclophilin A bound to a series of acylcic and macrocyclic inhibitors==		==Human cyclophilin A bound to a series of acylcic and macrocyclic inhibitors==
-	<StructureSection load='6x3y' size='340' side='right'caption='[[6x3y]]' scene=''>	+	<StructureSection load='6x3y' size='340' side='right'caption='[[6x3y]], [[Resolution\|resolution]] 1.40Å' 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=6X3Y OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6X3Y FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6x3y]] 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=6X3Y OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6X3Y 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=6x3y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6x3y OCA], [http://pdbe.org/6x3y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6x3y RCSB], [http://www.ebi.ac.uk/pdbsum/6x3y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6x3y ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UMM:tert-butyl+[(2S)-1-{[(3S,17S)-2,16-dioxo-10,15-dioxa-1,21-diazatricyclo[15.3.1.1~5,9~]docosa-5(22),6,8-trien-3-yl]amino}-3-methyl-1-oxobutan-2-yl]carbamate'>UMM</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6x3y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6x3y OCA], [http://pdbe.org/6x3y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6x3y RCSB], [http://www.ebi.ac.uk/pdbsum/6x3y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6x3y ProSAT]</span></td></tr>
	</table>		</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.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	A tremendous research and development effort was exerted toward combating chronic hepatitis C, ultimately leading to curative oral treatments, all of which are targeting viral proteins. Despite the advantage of numerous targets allowing for broad hepatitis C virus (HCV) genotype coverage, the only host target inhibitors that advanced into clinical development were Cyclosporin A based cyclophilin inhibitors. While cyclosporine-based molecules typically require a fermentation process, Gilead successfully pursued a fully synthetic, oral program based on Sanglifehrin A. The drug discovery process, though greatly helped by facile crystallography, was still hampered by the limitations in the accuracy of predictive computational methods for prioritizing compound ideas. Recent advances in accuracy and speed of free energy perturbation (FEP) methods, however, are attractive for prioritizing and de-risking synthetically challenging molecules and potentially could have had a significant impact on the speed of the development of this program. Here in our simulated prospective study, the binding free energies of 26 macrocyclic cyclophilin inhibitors were blindly predicted using FEP+ to test this hypothesis. The predictions had a low mean unsigned error (MUE) (1.1 kcal/mol) and accurately reproduced many design decisions from the program, suggesting that FEP+ has the potential to drive synthetic chemistry efforts by more accurately ranking compounds with non-intuitive structure-activity relationships (SAR).
		+
		+	Evaluation of Free Energy Calculations for the Prioritization of Macrocycle Synthesis.,Paulsen JL, Yu HS, Sindhikara D, Wang L, Appleby TC, Villasenor AG, Schmitz U, Shivakumar D J Chem Inf Model. 2020 Jun 15. doi: 10.1021/acs.jcim.0c00132. PMID:32539379<ref>PMID:32539379</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6x3y" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Cyclophilin 3D structures\|Cyclophilin 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Appleby TC]]	+	[[Category: Peptidylprolyl isomerase]]
-	[[Category: Paulsen JL]]	+	[[Category: Appleby, T C]]
-	[[Category: Schmitz U]]	+	[[Category: Paulsen, J L]]
-	[[Category: Shivakumar D]]	+	[[Category: Schmitz, U]]
		+	[[Category: Shivakumar, D]]
		+	[[Category: Cyclophilin some]]
		+	[[Category: Isomerase-isomerase inhibitor complex]]
		+	[[Category: Macrocylcic inhibitor]]
		+	[[Category: Peptidomimetic]]
		+	[[Category: Prolyl isomerase]]
		+	[[Category: Sanglifehrin some]]

OCA at 06:29, 25 June 2020

OCA — Thu, 25 Jun 2020 06:29:35 GMT

←Older revision		Revision as of 06:29, 25 June 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6x3y ~~is ON HOLD~~	+	==Human cyclophilin A bound to a series of acylcic and macrocyclic inhibitors==
-		+	<StructureSection load='6x3y' size='340' side='right'caption='[[6x3y]]' scene=''>
-	~~Authors~~: ~~Appleby~~, T.C., ~~Paulsen~~, J.L.~~, Schmitz, U~~., ~~Shivakumar~~, D.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6X3Y OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6X3Y FirstGlance]. <br>
-	~~Description: Human cyclophilin A bound to a series of acylcic and macrocyclic inhibitors~~	+	</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=6x3y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6x3y OCA], [http://pdbe.org/6x3y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6x3y RCSB], [http://www.ebi.ac.uk/pdbsum/6x3y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6x3y ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Shivakumar, D~~]]	+	__TOC__
-	[[Category: Paulsen~~, J.L~~]]	+	</StructureSection>
-	[[Category: Schmitz, U]]	+	[[Category: Large Structures]]
-	[[Category: ~~Appleby, T.C~~]]	+	[[Category: Appleby TC]]
		+	[[Category: Paulsen JL]]
		+	[[Category: Schmitz U]]
		+	[[Category: Shivakumar D]]

OCA: Protected "6x3y" [edit=sysop:move=sysop]

OCA — Wed, 27 May 2020 05:00:03 GMT

Protected "6x3y" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:00, 27 May 2020

OCA: New page: '''Unreleased structure''' The entry 6x3y is ON HOLD Authors: Appleby, T.C., Paulsen, J.L., Schmitz, U., Shivakumar, D. Description: Human cyclophilin A bound to a series of acylcic an...

OCA — Wed, 27 May 2020 05:00:00 GMT

New page: '''Unreleased structure''' The entry 6x3y is ON HOLD Authors: Appleby, T.C., Paulsen, J.L., Schmitz, U., Shivakumar, D. Description: Human cyclophilin A bound to a series of acylcic an...

New page

'''Unreleased structure'''

The entry 6x3y is ON HOLD

Authors: Appleby, T.C., Paulsen, J.L., Schmitz, U., Shivakumar, D.

Description: Human cyclophilin A bound to a series of acylcic and macrocyclic inhibitors
[[Category: Unreleased Structures]]
[[Category: Shivakumar, D]]
[[Category: Paulsen, J.L]]
[[Category: Schmitz, U]]
[[Category: Appleby, T.C]]