5qtu - Revision history

OCA at 11:27, 21 February 2024

OCA — Wed, 21 Feb 2024 11:27:56 GMT

←Older revision		Revision as of 11:27, 21 February 2024
Line 3:		Line 3:
	<StructureSection load='5qtu' size='340' side='right'caption='[[5qtu]], [[Resolution\|resolution]] 2.53Å' scene=''>		<StructureSection load='5qtu' size='340' side='right'caption='[[5qtu]], [[Resolution\|resolution]] 2.53Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5qtu]] 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=5QTU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5QTU FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5qtu]] 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=5QTU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5QTU 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=QEV:methyl+[(3R,7S)-7-{[1-(3-chloro-2-fluorophenyl)-5-methyl-1H-imidazole-4-carbonyl]amino}-3-methyl-2-oxo-2,3,4,5,6,7-hexahydro-1H-12,8-(metheno)-1,9-benzodiazacyclotetradecin-15-yl]carbamate'>QEV</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]] 2.53Å</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=QEV:methyl+[(3R,7S)-7-{[1-(3-chloro-2-fluorophenyl)-5-methyl-1H-imidazole-4-carbonyl]amino}-3-methyl-2-oxo-2,3,4,5,6,7-hexahydro-1H-12,8-(metheno)-1,9-benzodiazacyclotetradecin-15-yl]carbamate'>QEV</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=5qtu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5qtu OCA], [https://pdbe.org/5qtu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5qtu RCSB], [https://www.ebi.ac.uk/pdbsum/5qtu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5qtu 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=5qtu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5qtu OCA], [https://pdbe.org/5qtu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5qtu RCSB], [https://www.ebi.ac.uk/pdbsum/5qtu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5qtu 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 ==~~	+
-	Factor XIa inhibitors are promising novel anticoagulants which show excellent efficacy in preclinical thrombosis models with minimal effects on hemostasis. The discovery of potent and selective FXIa inhibitors which are also orally bioavailable has been a challenge. Here, we describe optimization of the imidazole-based macrocyclic series and our initial progress towards meeting this challenge. A two-pronged strategy, which focused on replacement of the imidazole scaffold and the design of new P1 groups, led to the discovery of potent, orally bioavailable pyridine-based macrocyclic FXIa inhibitors. Moreover, pyridine-based macrocycle 19, possessing the phenylimidazole carboxamide P1, exhibited excellent selectivity against relevant blood coagulation enzymes and displayed antithrombotic efficacy in a rabbit thrombosis model.	+

-	Potent, Orally Bioavailable and Efficacious Macrocyclic Inhibitors of Factor XIa. Discovery of Pyridine-Based Macrocycles Possessing Phenylazole Carboxamide P1 Groups.,Corte JR, Pinto DJP, Fang T, Osuna H, Yang W, Wang Y, Lai A, Clark C, Sun JH, Rampulla RA, Mathur A, Kaspady M, Neithnadka PR, Li YX, Rossi KA, Myers JE, Sheriff S, Lou Z, Harper TW, Huang CS, Zheng JJ, Bozarth JM, Wu Y, Wong PC, Crain E, Seiffert DA, Luettgen JM, Lam P, Wexler RR, Ewing WR J Med Chem. 2019 Dec 13. doi: 10.1021/acs.jmedchem.9b01768. PMID:31833761<ref>PMID:31833761</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 5qtu" 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 09:27, 12 May 2021

OCA — Wed, 12 May 2021 09:27:52 GMT

OCA at 16:03, 29 January 2020

OCA — Wed, 29 Jan 2020 16:03:06 GMT

←Older revision		Revision as of 16:03, 29 January 2020
Line 3:		Line 3:
	<StructureSection load='5qtu' size='340' side='right'caption='[[5qtu]], [[Resolution\|resolution]] 2.53Å' scene=''>		<StructureSection load='5qtu' size='340' side='right'caption='[[5qtu]], [[Resolution\|resolution]] 2.53Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5qtu]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5QTU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5QTU FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5qtu]] 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=5QTU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5QTU 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=QEV:methyl+[(3R,7S)-7-{[1-(3-chloro-2-fluorophenyl)-5-methyl-1H-imidazole-4-carbonyl]amino}-3-methyl-2-oxo-2,3,4,5,6,7-hexahydro-1H-12,8-(metheno)-1,9-benzodiazacyclotetradecin-15-yl]carbamate'>QEV</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=QEV:methyl+[(3R,7S)-7-{[1-(3-chloro-2-fluorophenyl)-5-methyl-1H-imidazole-4-carbonyl]amino}-3-methyl-2-oxo-2,3,4,5,6,7-hexahydro-1H-12,8-(metheno)-1,9-benzodiazacyclotetradecin-15-yl]carbamate'>QEV</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=5qtu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5qtu OCA], [http://pdbe.org/5qtu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5qtu RCSB], [http://www.ebi.ac.uk/pdbsum/5qtu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5qtu 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=5qtu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5qtu OCA], [http://pdbe.org/5qtu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5qtu RCSB], [http://www.ebi.ac.uk/pdbsum/5qtu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5qtu 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 09:01, 25 December 2019

OCA — Wed, 25 Dec 2019 09:01:03 GMT

←Older revision		Revision as of 09:01, 25 December 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5qtu is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==FACTOR XIA IN COMPLEX WITH THE INHIBITOR methyl [(3R,7S)-7-{[1-(3-chloro-2-fluorophenyl)-5-methyl-1H-imidazole-4-carbonyl]amino}-3-methyl-2-oxo-2,3,4,5,6,7-hexahydro-1H-12,8-(metheno)-1,9-benzodiazacyclotetradecin-15-yl]carbamate==
		+	<StructureSection load='5qtu' size='340' side='right'caption='[[5qtu]], [[Resolution\|resolution]] 2.53Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5qtu]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5QTU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5QTU 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=QEV:methyl+[(3R,7S)-7-{[1-(3-chloro-2-fluorophenyl)-5-methyl-1H-imidazole-4-carbonyl]amino}-3-methyl-2-oxo-2,3,4,5,6,7-hexahydro-1H-12,8-(metheno)-1,9-benzodiazacyclotetradecin-15-yl]carbamate'>QEV</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=5qtu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5qtu OCA], [http://pdbe.org/5qtu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5qtu RCSB], [http://www.ebi.ac.uk/pdbsum/5qtu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5qtu 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 ==
		+	Factor XIa inhibitors are promising novel anticoagulants which show excellent efficacy in preclinical thrombosis models with minimal effects on hemostasis. The discovery of potent and selective FXIa inhibitors which are also orally bioavailable has been a challenge. Here, we describe optimization of the imidazole-based macrocyclic series and our initial progress towards meeting this challenge. A two-pronged strategy, which focused on replacement of the imidazole scaffold and the design of new P1 groups, led to the discovery of potent, orally bioavailable pyridine-based macrocyclic FXIa inhibitors. Moreover, pyridine-based macrocycle 19, possessing the phenylimidazole carboxamide P1, exhibited excellent selectivity against relevant blood coagulation enzymes and displayed antithrombotic efficacy in a rabbit thrombosis model.

-	~~Authors: Sheriff~~, S.	+	Potent, Orally Bioavailable and Efficacious Macrocyclic Inhibitors of Factor XIa. Discovery of Pyridine-Based Macrocycles Possessing Phenylazole Carboxamide P1 Groups.,Corte JR, Pinto DJP, Fang T, Osuna H, Yang W, Wang Y, Lai A, Clark C, Sun JH, Rampulla RA, Mathur A, Kaspady M, Neithnadka PR, Li YX, Rossi KA, Myers JE, Sheriff S, Lou Z, Harper TW, Huang CS, Zheng JJ, Bozarth JM, Wu Y, Wong PC, Crain E, Seiffert DA, Luettgen JM, Lam P, Wexler RR, Ewing WR J Med Chem. 2019 Dec 13. doi: 10.1021/acs.jmedchem.9b01768. PMID:31833761<ref>PMID:31833761</ref>

-	~~Description: FACTOR XIA IN COMPLEX WITH THE INHIBITOR methyl [(3R~~,~~7S)~~-7-{[~~1-(3-chloro-2-fluorophenyl)-5-methyl-1H-imidazole-4-carbonyl~~]~~amino}-3-methyl-2-oxo-2,3,4,5,6,7-hexahydro-1H-12,8-(metheno)-1,9-benzodiazacyclotetradecin-15-yl~~]~~carbamate~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 5qtu" 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 04:54, 6 November 2019

OCA — Wed, 06 Nov 2019 04:54:36 GMT

←Older revision		Revision as of 04:54, 6 November 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

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

-	Description: FACTOR XIA IN COMPLEX WITH THE INHIBITOR ~~METHYL~~ (~~(10R~~,~~14S~~)-14-~~(((~~1-(3-~~CHLORO~~-2-~~FLUOROPHENYL~~)-5-~~METHYL~~-1H-~~IMIDAZOL~~-4-~~YL)CARBONYL)AMINO)~~-10-~~METHYL~~-9-~~OXO~~-8,~~16-DIAZATRICYCLO[13.~~3~~.1.0~2~~,~~7~]NONADECA-1(19)~~,~~2,4~~,6,15,17-~~HEXAEN~~-5-~~YL)CARBAMATE~~	+	Description: FACTOR XIA IN COMPLEX WITH THE INHIBITOR methyl [(3R,7S)-7-{[1-(3-chloro-2-fluorophenyl)-5-methyl-1H-imidazole-4-carbonyl]amino}-3-methyl-2-oxo-2,3,4,5,6,7-hexahydro-1H-12,8-(metheno)-1,9-benzodiazacyclotetradecin-15-yl]carbamate
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Sheriff, S]]		[[Category: Sheriff, S]]

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

OCA — Wed, 23 Oct 2019 04:46:44 GMT

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

←Older revision

Revision as of 04:46, 23 October 2019

OCA: New page: '''Unreleased structure''' The entry 5qtu is ON HOLD Authors: Sheriff, S. Description: FACTOR XIA IN COMPLEX WITH THE INHIBITOR METHYL ((10R,14S)-14-(((1-(3-CHLORO-2-FLUOROPHENYL)-5-ME...

OCA — Wed, 23 Oct 2019 04:46:42 GMT

New page: '''Unreleased structure''' The entry 5qtu is ON HOLD Authors: Sheriff, S. Description: FACTOR XIA IN COMPLEX WITH THE INHIBITOR METHYL ((10R,14S)-14-(((1-(3-CHLORO-2-FLUOROPHENYL)-5-ME...

New page

'''Unreleased structure'''

The entry 5qtu is ON HOLD

Authors: Sheriff, S.

Description: FACTOR XIA IN COMPLEX WITH THE INHIBITOR METHYL ((10R,14S)-14-(((1-(3-CHLORO-2-FLUOROPHENYL)-5-METHYL-1H-IMIDAZOL-4-YL)CARBONYL)AMINO)-10-METHYL-9-OXO-8,16-DIAZATRICYCLO[13.3.1.0~2,7~]NONADECA-1(19),2,4,6,15,17-HEXAEN-5-YL)CARBAMATE
[[Category: Unreleased Structures]]
[[Category: Sheriff, S]]

←Older revision		Revision as of 09:27, 12 May 2021
Line 3:		Line 3:
	<StructureSection load='5qtu' size='340' side='right'caption='[[5qtu]], [[Resolution\|resolution]] 2.53Å' scene=''>		<StructureSection load='5qtu' size='340' side='right'caption='[[5qtu]], [[Resolution\|resolution]] 2.53Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5qtu]] 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=5QTU OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5QTU FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5qtu]] 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=5QTU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5QTU 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=QEV:methyl+[(3R,7S)-7-{[1-(3-chloro-2-fluorophenyl)-5-methyl-1H-imidazole-4-carbonyl]amino}-3-methyl-2-oxo-2,3,4,5,6,7-hexahydro-1H-12,8-(metheno)-1,9-benzodiazacyclotetradecin-15-yl]carbamate'>QEV</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=QEV:methyl+[(3R,7S)-7-{[1-(3-chloro-2-fluorophenyl)-5-methyl-1H-imidazole-4-carbonyl]amino}-3-methyl-2-oxo-2,3,4,5,6,7-hexahydro-1H-12,8-(metheno)-1,9-benzodiazacyclotetradecin-15-yl]carbamate'>QEV</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=5qtu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5qtu OCA], [~~http~~://pdbe.org/5qtu PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5qtu RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5qtu PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5qtu 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=5qtu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5qtu OCA], [https://pdbe.org/5qtu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5qtu RCSB], [https://www.ebi.ac.uk/pdbsum/5qtu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5qtu 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 ==