5qtx - Revision history

OCA at 11:28, 21 February 2024

2024-02-21T11:28:00Z

←Older revision		Revision as of 11:28, 21 February 2024
Line 3:		Line 3:
	<StructureSection load='5qtx' size='340' side='right'caption='[[5qtx]], [[Resolution\|resolution]] 2.07Å' scene=''>		<StructureSection load='5qtx' size='340' side='right'caption='[[5qtx]], [[Resolution\|resolution]] 2.07Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5qtx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5QTX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5QTX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5qtx]] is a 2 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=5QTX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5QTX FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=QLD:ethyl+(2R,7S)-7-({(2E)-3-[5-chloro-2-(1H-tetrazol-1-yl)phenyl]prop-2-enoyl}amino)-14-[(methoxycarbonyl)amino]-1,2,3,4,5,6,7,9-octahydro-11,8-(azeno)-1,9-benzodiazacyclotridecine-2-carboxylate'>QLD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.07Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">F11 ([https://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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=QLD:ethyl+(2R,7S)-7-({(2E)-3-[5-chloro-2-(1H-tetrazol-1-yl)phenyl]prop-2-enoyl}amino)-14-[(methoxycarbonyl)amino]-1,2,3,4,5,6,7,9-octahydro-11,8-(azeno)-1,9-benzodiazacyclotridecine-2-carboxylate'>QLD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Coagulation_factor_XIa Coagulation factor XIa], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.27 3.4.21.27] </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=5qtx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5qtx OCA], [https://pdbe.org/5qtx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5qtx RCSB], [https://www.ebi.ac.uk/pdbsum/5qtx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5qtx 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=5qtx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5qtx OCA], [https://pdbe.org/5qtx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5qtx RCSB], [https://www.ebi.ac.uk/pdbsum/5qtx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5qtx ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/FA11_HUMAN FA11_HUMAN]] Defects in F11 are the cause of factor XI deficiency (FA11D) [MIM:[https://omim.org/entry/612416 612416]]; also known as plasma thromboplastin antecedent deficiency or Rosenthal syndrome. It is a hemorrhagic disease characterized by reduced levels and activity of factor XI resulting in moderate bleeding symptoms, usually occurring after trauma or surgery. Patients usually do not present spontaneous bleeding but women can present with menorrhagia. Hemorrhages are usually moderate.<ref>PMID:2813350</ref> <ref>PMID:1547342</ref> <ref>PMID:7888672</ref> <ref>PMID:7669672</ref> <ref>PMID:9401068</ref> <ref>PMID:9787168</ref> <ref>PMID:10027710</ref> <ref>PMID:10606881</ref> <ref>PMID:11895778</ref> <ref>PMID:15026311</ref> <ref>PMID:15180874</ref> <ref>PMID:15953011</ref> <ref>PMID:16607084</ref> <ref>PMID:18005151</ref> <ref>PMID:21668437</ref> <ref>PMID:21457405</ref> <ref>PMID:22016685</ref> <ref>PMID:22322133</ref> <ref>PMID:21999818</ref> <ref>PMID:22159456</ref>	+	[https://www.uniprot.org/uniprot/FA11_HUMAN FA11_HUMAN] Defects in F11 are the cause of factor XI deficiency (FA11D) [MIM:[https://omim.org/entry/612416 612416]; also known as plasma thromboplastin antecedent deficiency or Rosenthal syndrome. It is a hemorrhagic disease characterized by reduced levels and activity of factor XI resulting in moderate bleeding symptoms, usually occurring after trauma or surgery. Patients usually do not present spontaneous bleeding but women can present with menorrhagia. Hemorrhages are usually moderate.<ref>PMID:2813350</ref> <ref>PMID:1547342</ref> <ref>PMID:7888672</ref> <ref>PMID:7669672</ref> <ref>PMID:9401068</ref> <ref>PMID:9787168</ref> <ref>PMID:10027710</ref> <ref>PMID:10606881</ref> <ref>PMID:11895778</ref> <ref>PMID:15026311</ref> <ref>PMID:15180874</ref> <ref>PMID:15953011</ref> <ref>PMID:16607084</ref> <ref>PMID:18005151</ref> <ref>PMID:21668437</ref> <ref>PMID:21457405</ref> <ref>PMID:22016685</ref> <ref>PMID:22322133</ref> <ref>PMID:21999818</ref> <ref>PMID:22159456</ref>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/FA11_HUMAN FA11_HUMAN]] Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX.	+	[https://www.uniprot.org/uniprot/FA11_HUMAN FA11_HUMAN] Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX.
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	The discovery of orally bioavailable FXIa inhibitors has been a challenge. Herein, we describe our efforts to address this challenge by optimization of our imidazole-based macrocyclic series. Our optimization strategy focused on modifications to the P2 prime, macrocyclic amide linker, and the imidazole scaffold. Replacing the amide of the macrocyclic linker with amide isosteres led to the discovery of substituted amine linkers which not only maintained FXIa binding affinity but also improved oral exposure in rats. Combining the optimized macrocyclic amine linker with a pyridine scaffold afforded compounds 23 and 24 that were orally bioavailable, single-digit nanomolar FXIa inhibitors with excellent selectivity against relevant blood coagulation enzymes.	+

-	Orally bioavailable amine-linked macrocyclic inhibitors of factor XIa.,Fang T, Corte JR, Gilligan PJ, Jeon Y, Osuna H, Rossi KA, Myers JE Jr, Sheriff S, Lou Z, Zheng JJ, Harper TW, Bozarth JM, Wu Y, Luettgen JM, Seiffert DA, Wexler RR, Lam PYS Bioorg Med Chem Lett. 2020 Feb 15;30(4):126949. doi: 10.1016/j.bmcl.2020.126949. , Epub 2020 Jan 7. PMID:31932224<ref>PMID:31932224</ref>	+	==See Also==
-		+	*[[Factor XIa 3D structures\|Factor XIa 3D structures]]
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class~~=~~"pdbe-citations 5qtx" style~~=~~"background-color:#fffaf0;"></div>~~	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Coagulation factor XIa]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Human~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Sheriff, S]]	+	[[Category: Sheriff S]]
-	~~[[Category: Blood coagulation factor]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Protein inhibitor complex]]~~	+
-	~~[[Category: Serine protease~~]]	+

OCA at 09:28, 12 May 2021

2021-05-12T09:28:06Z

OCA at 10:13, 26 February 2020

2020-02-26T10:13:57Z

←Older revision		Revision as of 10:13, 26 February 2020
Line 3:		Line 3:
	<StructureSection load='5qtx' size='340' side='right'caption='[[5qtx]], [[Resolution\|resolution]] 2.07Å' scene=''>		<StructureSection load='5qtx' size='340' side='right'caption='[[5qtx]], [[Resolution\|resolution]] 2.07Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5qtx]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5QTX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5QTX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5qtx]] is a 2 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=5QTX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5QTX FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=QLD:ethyl+(2R,7S)-7-({(2E)-3-[5-chloro-2-(1H-tetrazol-1-yl)phenyl]prop-2-enoyl}amino)-14-[(methoxycarbonyl)amino]-1,2,3,4,5,6,7,9-octahydro-11,8-(azeno)-1,9-benzodiazacyclotridecine-2-carboxylate'>QLD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=QLD:ethyl+(2R,7S)-7-({(2E)-3-[5-chloro-2-(1H-tetrazol-1-yl)phenyl]prop-2-enoyl}amino)-14-[(methoxycarbonyl)amino]-1,2,3,4,5,6,7,9-octahydro-11,8-(azeno)-1,9-benzodiazacyclotridecine-2-carboxylate'>QLD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">F11 ([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/Coagulation_factor_XIa Coagulation factor XIa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.27 3.4.21.27] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Coagulation_factor_XIa Coagulation factor XIa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.27 3.4.21.27] </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=5qtx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5qtx OCA], [http://pdbe.org/5qtx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5qtx RCSB], [http://www.ebi.ac.uk/pdbsum/5qtx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5qtx 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=5qtx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5qtx OCA], [http://pdbe.org/5qtx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5qtx RCSB], [http://www.ebi.ac.uk/pdbsum/5qtx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5qtx ProSAT]</span></td></tr>
Line 26:		Line 27:
	</StructureSection>		</StructureSection>
	[[Category: Coagulation factor XIa]]		[[Category: Coagulation factor XIa]]
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Sheriff, S]]		[[Category: Sheriff, S]]

OCA at 15:23, 29 January 2020

2020-01-29T15:23:25Z

←Older revision		Revision as of 15:23, 29 January 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5qtx is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==FACTOR XIA IN COMPLEX WITH THE INHIBITOR ethyl (2R,7S)-7-({(2E)-3-[5-chloro-2-(1H-tetrazol-1-yl)phenyl]prop-2-enoyl}amino)-14-[(methoxycarbonyl)amino]-1,2,3,4,5,6,7,9-octahydro-11,8-(azeno)-1,9-benzodiazacyclotridecine-2-carboxylate==
		+	<StructureSection load='5qtx' size='340' side='right'caption='[[5qtx]], [[Resolution\|resolution]] 2.07Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5qtx]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5QTX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5QTX FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=QLD:ethyl+(2R,7S)-7-({(2E)-3-[5-chloro-2-(1H-tetrazol-1-yl)phenyl]prop-2-enoyl}amino)-14-[(methoxycarbonyl)amino]-1,2,3,4,5,6,7,9-octahydro-11,8-(azeno)-1,9-benzodiazacyclotridecine-2-carboxylate'>QLD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Coagulation_factor_XIa Coagulation factor XIa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.27 3.4.21.27] </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=5qtx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5qtx OCA], [http://pdbe.org/5qtx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5qtx RCSB], [http://www.ebi.ac.uk/pdbsum/5qtx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5qtx ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/FA11_HUMAN FA11_HUMAN]] Defects in F11 are the cause of factor XI deficiency (FA11D) [MIM:[http://omim.org/entry/612416 612416]]; also known as plasma thromboplastin antecedent deficiency or Rosenthal syndrome. It is a hemorrhagic disease characterized by reduced levels and activity of factor XI resulting in moderate bleeding symptoms, usually occurring after trauma or surgery. Patients usually do not present spontaneous bleeding but women can present with menorrhagia. Hemorrhages are usually moderate.<ref>PMID:2813350</ref> <ref>PMID:1547342</ref> <ref>PMID:7888672</ref> <ref>PMID:7669672</ref> <ref>PMID:9401068</ref> <ref>PMID:9787168</ref> <ref>PMID:10027710</ref> <ref>PMID:10606881</ref> <ref>PMID:11895778</ref> <ref>PMID:15026311</ref> <ref>PMID:15180874</ref> <ref>PMID:15953011</ref> <ref>PMID:16607084</ref> <ref>PMID:18005151</ref> <ref>PMID:21668437</ref> <ref>PMID:21457405</ref> <ref>PMID:22016685</ref> <ref>PMID:22322133</ref> <ref>PMID:21999818</ref> <ref>PMID:22159456</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/FA11_HUMAN FA11_HUMAN]] Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The discovery of orally bioavailable FXIa inhibitors has been a challenge. Herein, we describe our efforts to address this challenge by optimization of our imidazole-based macrocyclic series. Our optimization strategy focused on modifications to the P2 prime, macrocyclic amide linker, and the imidazole scaffold. Replacing the amide of the macrocyclic linker with amide isosteres led to the discovery of substituted amine linkers which not only maintained FXIa binding affinity but also improved oral exposure in rats. Combining the optimized macrocyclic amine linker with a pyridine scaffold afforded compounds 23 and 24 that were orally bioavailable, single-digit nanomolar FXIa inhibitors with excellent selectivity against relevant blood coagulation enzymes.

-	~~Authors: Sheriff~~, S.	+	Orally bioavailable amine-linked macrocyclic inhibitors of factor XIa.,Fang T, Corte JR, Gilligan PJ, Jeon Y, Osuna H, Rossi KA, Myers JE Jr, Sheriff S, Lou Z, Zheng JJ, Harper TW, Bozarth JM, Wu Y, Luettgen JM, Seiffert DA, Wexler RR, Lam PYS Bioorg Med Chem Lett. 2020 Feb 15;30(4):126949. doi: 10.1016/j.bmcl.2020.126949. , Epub 2020 Jan 7. PMID:31932224<ref>PMID:31932224</ref>

-	~~Description: FACTOR XIA IN COMPLEX WITH THE INHIBITOR ethyl (2R~~,~~7S)~~-~~7-({(2E)-3~~-[~~5-chloro-2-(1H-tetrazol-1-yl)phenyl]prop-2-enoyl}amino)-14-~~[~~(methoxycarbonyl)amino~~]~~-1,2,3,4,5,6,7,9-octahydro-11,8-(azeno)-1,9-benzodiazacyclotridecine-2-carboxylate~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 5qtx" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Coagulation factor XIa]]
		+	[[Category: Large Structures]]
	[[Category: Sheriff, S]]		[[Category: Sheriff, S]]
		+	[[Category: Blood coagulation factor]]
		+	[[Category: Hydrolase]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Protein inhibitor complex]]
		+	[[Category: Serine protease]]

OCA at 05:30, 18 December 2019

2019-12-18T05:30:52Z

←Older revision		Revision as of 05:30, 18 December 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5qtx is ON HOLD	+	The entry 5qtx is ON HOLD until Paper Publication

	Authors: Sheriff, S.		Authors: Sheriff, S.

OCA at 04:59, 27 November 2019

2019-11-27T04:59:07Z

←Older revision		Revision as of 04:59, 27 November 2019
Line 5:		Line 5:
	Authors: Sheriff, S.		Authors: Sheriff, S.

-	Description: FACTOR XIA IN COMPLEX WITH THE INHIBITOR ~~ETHYL~~ (9R,~~14S~~)-14-(((2E)-3-(5-~~CHLORO~~-2-(1H-~~TETRAZOL~~-1-~~YL)PHENYL~~)-2-~~PROPENOYL)AMINO~~)-5-(~~(METHOXYCARBONYL~~)~~AMINO)-8,16,18-TRIAZATRICYCLO[13.2.1.0~2,7~~~]~~OCTADECA~~-1~~(17)~~,2,4,6,15(18)-~~PENTAENE-~~9-~~CARBOXYLATE~~	+	Description: FACTOR XIA IN COMPLEX WITH THE INHIBITOR ethyl (2R,7S)-7-({(2E)-3-[5-chloro-2-(1H-tetrazol-1-yl)phenyl]prop-2-enoyl}amino)-14-[(methoxycarbonyl)amino]-1,2,3,4,5,6,7,9-octahydro-11,8-(azeno)-1,9-benzodiazacyclotridecine-2-carboxylate
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Sheriff, S]]		[[Category: Sheriff, S]]

OCA: Protected "5qtx" [edit=sysop:move=sysop]

2019-11-20T13:20:37Z

Protected "5qtx" [edit=sysop:move=sysop]

←Older revision

Revision as of 13:20, 20 November 2019

OCA: New page: '''Unreleased structure''' The entry 5qtx is ON HOLD Authors: Sheriff, S. Description: FACTOR XIA IN COMPLEX WITH THE INHIBITOR ETHYL (9R,14S)-14-(((2E)-3-(5-CHLORO-2-(1H-TETRAZOL-1-YL...

2019-11-20T13:20:36Z

New page: '''Unreleased structure''' The entry 5qtx is ON HOLD Authors: Sheriff, S. Description: FACTOR XIA IN COMPLEX WITH THE INHIBITOR ETHYL (9R,14S)-14-(((2E)-3-(5-CHLORO-2-(1H-TETRAZOL-1-YL...

New page

'''Unreleased structure'''

The entry 5qtx is ON HOLD

Authors: Sheriff, S.

Description: FACTOR XIA IN COMPLEX WITH THE INHIBITOR ETHYL (9R,14S)-14-(((2E)-3-(5-CHLORO-2-(1H-TETRAZOL-1-YL)PHENYL)-2-PROPENOYL)AMINO)-5-((METHOXYCARBONYL)AMINO)-8,16,18-TRIAZATRICYCLO[13.2.1.0~2,7~]OCTADECA-1(17),2,4,6,15(18)-PENTAENE-9-CARBOXYLATE
[[Category: Unreleased Structures]]
[[Category: Sheriff, S]]

←Older revision		Revision as of 09:28, 12 May 2021
Line 3:		Line 3:
	<StructureSection load='5qtx' size='340' side='right'caption='[[5qtx]], [[Resolution\|resolution]] 2.07Å' scene=''>		<StructureSection load='5qtx' size='340' side='right'caption='[[5qtx]], [[Resolution\|resolution]] 2.07Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5qtx]] is a 2 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=5QTX OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5QTX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5qtx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5QTX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5QTX FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=QLD:ethyl+(2R,7S)-7-({(2E)-3-[5-chloro-2-(1H-tetrazol-1-yl)phenyl]prop-2-enoyl}amino)-14-[(methoxycarbonyl)amino]-1,2,3,4,5,6,7,9-octahydro-11,8-(azeno)-1,9-benzodiazacyclotridecine-2-carboxylate'>QLD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=QLD:ethyl+(2R,7S)-7-({(2E)-3-[5-chloro-2-(1H-tetrazol-1-yl)phenyl]prop-2-enoyl}amino)-14-[(methoxycarbonyl)amino]-1,2,3,4,5,6,7,9-octahydro-11,8-(azeno)-1,9-benzodiazacyclotridecine-2-carboxylate'>QLD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">F11 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">F11 ([https://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/Coagulation_factor_XIa Coagulation factor XIa], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.27 3.4.21.27] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Coagulation_factor_XIa Coagulation factor XIa], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.27 3.4.21.27] </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=5qtx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5qtx OCA], [~~http~~://pdbe.org/5qtx PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5qtx RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5qtx PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5qtx 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=5qtx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5qtx OCA], [https://pdbe.org/5qtx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5qtx RCSB], [https://www.ebi.ac.uk/pdbsum/5qtx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5qtx ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/FA11_HUMAN FA11_HUMAN]] Defects in F11 are the cause of factor XI deficiency (FA11D) [MIM:[~~http~~://omim.org/entry/612416 612416]]; also known as plasma thromboplastin antecedent deficiency or Rosenthal syndrome. It is a hemorrhagic disease characterized by reduced levels and activity of factor XI resulting in moderate bleeding symptoms, usually occurring after trauma or surgery. Patients usually do not present spontaneous bleeding but women can present with menorrhagia. Hemorrhages are usually moderate.<ref>PMID:2813350</ref> <ref>PMID:1547342</ref> <ref>PMID:7888672</ref> <ref>PMID:7669672</ref> <ref>PMID:9401068</ref> <ref>PMID:9787168</ref> <ref>PMID:10027710</ref> <ref>PMID:10606881</ref> <ref>PMID:11895778</ref> <ref>PMID:15026311</ref> <ref>PMID:15180874</ref> <ref>PMID:15953011</ref> <ref>PMID:16607084</ref> <ref>PMID:18005151</ref> <ref>PMID:21668437</ref> <ref>PMID:21457405</ref> <ref>PMID:22016685</ref> <ref>PMID:22322133</ref> <ref>PMID:21999818</ref> <ref>PMID:22159456</ref>	+	[[https://www.uniprot.org/uniprot/FA11_HUMAN FA11_HUMAN]] Defects in F11 are the cause of factor XI deficiency (FA11D) [MIM:[https://omim.org/entry/612416 612416]]; also known as plasma thromboplastin antecedent deficiency or Rosenthal syndrome. It is a hemorrhagic disease characterized by reduced levels and activity of factor XI resulting in moderate bleeding symptoms, usually occurring after trauma or surgery. Patients usually do not present spontaneous bleeding but women can present with menorrhagia. Hemorrhages are usually moderate.<ref>PMID:2813350</ref> <ref>PMID:1547342</ref> <ref>PMID:7888672</ref> <ref>PMID:7669672</ref> <ref>PMID:9401068</ref> <ref>PMID:9787168</ref> <ref>PMID:10027710</ref> <ref>PMID:10606881</ref> <ref>PMID:11895778</ref> <ref>PMID:15026311</ref> <ref>PMID:15180874</ref> <ref>PMID:15953011</ref> <ref>PMID:16607084</ref> <ref>PMID:18005151</ref> <ref>PMID:21668437</ref> <ref>PMID:21457405</ref> <ref>PMID:22016685</ref> <ref>PMID:22322133</ref> <ref>PMID:21999818</ref> <ref>PMID:22159456</ref>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/FA11_HUMAN FA11_HUMAN]] Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX.	+	[[https://www.uniprot.org/uniprot/FA11_HUMAN FA11_HUMAN]] Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==