7thd - Revision history

OCA at 17:04, 18 October 2023

2023-10-18T17:04:28Z

← Older revision		Revision as of 17:04, 18 October 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7thd]] 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=7THD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7THD FirstGlance]. <br>		<table><tr><td colspan='2'>[[7thd]] 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=7THD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7THD FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=I4V:[(4-{[(4S,7S,11R,13E,19S)-19-{[2-(2-aminoethoxy)ethyl]carbamoyl}-7-benzyl-3,6,12,15,21-pentaoxo-1,3,4,5,6,7,8,9,10,12,15,16,17,18,19,20,21,22-octadecahydro-2H-7,11-methano-2,5,11,16,20-benzopentaazacyclotetracosin-4-yl]methyl}[1,1-biphenyl]-4-yl)methyl]propanedioic+acid'>I4V</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]] 1.16Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=I4V:[(4-{[(4S,7S,11R,13E,19S)-19-{[2-(2-aminoethoxy)ethyl]carbamoyl}-7-benzyl-3,6,12,15,21-pentaoxo-1,3,4,5,6,7,8,9,10,12,15,16,17,18,19,20,21,22-octadecahydro-2H-7,11-methano-2,5,11,16,20-benzopentaazacyclotetracosin-4-yl]methyl}[1,1-biphenyl]-4-yl)methyl]propanedioic+acid'>I4V</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=7thd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7thd OCA], [https://pdbe.org/7thd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7thd RCSB], [https://www.ebi.ac.uk/pdbsum/7thd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7thd ProSAT]</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=7thd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7thd OCA], [https://pdbe.org/7thd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7thd RCSB], [https://www.ebi.ac.uk/pdbsum/7thd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7thd ProSAT]</span></td></tr>
	</table>		</table>
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	</div>		</div>
	<div class="pdbe-citations 7thd" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7thd" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Cyclophilin 3D structures\|Cyclophilin 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:33, 3 November 2022

2022-11-03T07:33:54Z

← Older revision		Revision as of 07:33, 3 November 2022
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	==Structure of Cyclophilin D Peptidyl-Prolyl Isomerase Domain bound to Macrocyclic Inhibitor B52==		==Structure of Cyclophilin D Peptidyl-Prolyl Isomerase Domain bound to Macrocyclic Inhibitor B52==
	<StructureSection load='7thd' size='340' side='right'caption='[[7thd]]' scene=''>		<StructureSection load='7thd' size='340' side='right'caption='[[7thd]], [[Resolution\|resolution]] 1.16Å' 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=7THD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7THD FirstGlance]. <br>		<table><tr><td colspan='2'>[[7thd]] 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=7THD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7THD 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=7thd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7thd OCA], [https://pdbe.org/7thd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7thd RCSB], [https://www.ebi.ac.uk/pdbsum/7thd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7thd 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=I4V:[(4-{[(4S,7S,11R,13E,19S)-19-{[2-(2-aminoethoxy)ethyl]carbamoyl}-7-benzyl-3,6,12,15,21-pentaoxo-1,3,4,5,6,7,8,9,10,12,15,16,17,18,19,20,21,22-octadecahydro-2H-7,11-methano-2,5,11,16,20-benzopentaazacyclotetracosin-4-yl]methyl}[1,1-biphenyl]-4-yl)methyl]propanedioic+acid'>I4V</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=7thd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7thd OCA], [https://pdbe.org/7thd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7thd RCSB], [https://www.ebi.ac.uk/pdbsum/7thd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7thd ProSAT]</span></td></tr>
	</table>		</table>
			== Function ==
			[https://www.uniprot.org/uniprot/PPIF_HUMAN PPIF_HUMAN] PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Involved in regulation of the mitochondrial permeability transition pore (mPTP). It is proposed that its association with the mPTP is masking a binding site for inhibiting inorganic phosphate (Pi) and promotes the open probablity of the mPTP leading to apoptosis or necrosis; the requirement of the PPIase activity for this function is debated. In cooperation with mitochondrial TP53 is involved in activating oxidative stress-induced necrosis. Involved in modulation of mitochondrial membrane F(1)F(0) ATP synthase activity and regulation of mitochondrial matrix adenine nucleotide levels. Has anti-apoptotic activity independently of mPTP and in cooperation with BCL2 inhibits cytochrome c-dependent apoptosis.<ref>PMID:19228691</ref> <ref>PMID:22726440</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Although cyclophilins are attractive targets for probing biology and therapeutic intervention, no subtype-selective cyclophilin inhibitors have been described. We discovered novel cyclophilin inhibitors from the in vitro selection of a DNA-templated library of 256,000 drug-like macrocycles for cyclophilin D (CypD) affinity. Iterated macrocycle engineering guided by ten X-ray co-crystal structures yielded potent and selective inhibitors (half maximal inhibitory concentration (IC50) = 10 nM) that bind the active site of CypD and also make novel interactions with non-conserved residues in the S2 pocket, an adjacent exo-site. The resulting macrocycles inhibit CypD activity with 21- to >10,000-fold selectivity over other cyclophilins and inhibit mitochondrial permeability transition pore opening in isolated mitochondria. We further exploited S2 pocket interactions to develop the first cyclophilin E (CypE)-selective inhibitor, which forms a reversible covalent bond with a CypE S2 pocket lysine, and exhibits 30- to >4,000-fold selectivity over other cyclophilins. These findings reveal a strategy to generate isoform-selective small-molecule cyclophilin modulators, advancing their suitability as targets for biological investigation and therapeutic development.

			Discovery and molecular basis of subtype-selective cyclophilin inhibitors.,Peterson AA, Rangwala AM, Thakur MK, Ward PS, Hung C, Outhwaite IR, Chan AI, Usanov DL, Mootha VK, Seeliger MA, Liu DR Nat Chem Biol. 2022 Nov;18(11):1184-1195. doi: 10.1038/s41589-022-01116-1. Epub, 2022 Sep 26. PMID:36163383<ref>PMID:36163383</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 7thd" style="background-color:#fffaf0;"></div>
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Liu DR]]		[[Category: Liu DR]]

OCA at 04:49, 25 August 2022

2022-08-25T04:49:35Z

← Older revision		Revision as of 04:49, 25 August 2022
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	~~'''Unreleased structure'''~~

	~~The entry~~ 7thd is ~~ON HOLD until Paper Publication~~		==Structure of Cyclophilin D Peptidyl-Prolyl Isomerase Domain bound to Macrocyclic Inhibitor B52==
			<StructureSection load='7thd' size='340' side='right'caption='[[7thd]]' scene=''>
	~~Authors~~: ~~Rangwala, A~~.M., ~~Thakur, M~~.K., ~~Seeliger~~, M.A., ~~Peterson, A~~.A., ~~Liu, D~~.R.		== Structural highlights ==
			<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7THD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7THD FirstGlance]. <br>
	~~Description: Structure of Cyclophilin D Peptidyl-Prolyl Isomerase Domain bound to Macrocyclic Inhibitor B52~~		</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=7thd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7thd OCA], [https://pdbe.org/7thd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7thd RCSB], [https://www.ebi.ac.uk/pdbsum/7thd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7thd ProSAT]</span></td></tr>
	[[Category: ~~Unreleased~~ Structures]]		</table>
	[[Category: ~~Peterson, A.A~~]]		__TOC__
	[[Category: ~~Seeliger, M.A~~]]		</StructureSection>
	[[Category: ~~Liu, D.R~~]]		[[Category: Large Structures]]
	[[Category: ~~Thakur, M.K~~]]		[[Category: Liu DR]]
	[[Category: ~~Rangwala, A.M~~]]		[[Category: Peterson AA]]
			[[Category: Rangwala AM]]
			[[Category: Seeliger MA]]
			[[Category: Thakur MK]]

OCA: Protected "7thd" [edit=sysop:move=sysop]

2022-01-19T06:02:39Z

Protected "7thd" [edit=sysop:move=sysop]

← Older revision	Revision as of 06:02, 19 January 2022
(No difference)

OCA: New page: '''Unreleased structure''' The entry 7thd is ON HOLD until Paper Publication Authors: Rangwala, A.M., Thakur, M.K., Seeliger, M.A., Peterson, A.A., Liu, D.R. Description: Structure of ...

2022-01-19T06:02:38Z

New page: '''Unreleased structure''' The entry 7thd is ON HOLD until Paper Publication Authors: Rangwala, A.M., Thakur, M.K., Seeliger, M.A., Peterson, A.A., Liu, D.R. Description: Structure of ...

New page

'''Unreleased structure'''

The entry 7thd is ON HOLD until Paper Publication

Authors: Rangwala, A.M., Thakur, M.K., Seeliger, M.A., Peterson, A.A., Liu, D.R.

Description: Structure of Cyclophilin D Peptidyl-Prolyl Isomerase Domain bound to Macrocyclic Inhibitor B52
[[Category: Unreleased Structures]]
[[Category: Peterson, A.A]]
[[Category: Seeliger, M.A]]
[[Category: Liu, D.R]]
[[Category: Thakur, M.K]]
[[Category: Rangwala, A.M]]