Factor XIa - Revision history

Michal Harel at 10:05, 27 February 2023

2023-02-27T10:05:59Z

←Older revision		Revision as of 10:05, 27 February 2023
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	</StructureSection>		</StructureSection>

-
-	==3D structures of Factor XIa==
-
-	Updated on {{REVISIONDAY2}}-{{MONTHNAME\|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
-	{{#tree:id=OrganizedByTopic\|openlevels=0\|
-
-	*Factor XIa
-	**[[2j8j]], [[2j8l]] – hFXIa A4 domain (residues 290-379) – human – NMR<br />
-	**[[2f83]], [[6i58]] - hFXIa zymogen (residues 1-625)
-
-	*Factor XIa light chain catalytic domain (residues 388-625) inhibitor complex
-
-	**[[3bg8]] – hFXIa + clavatadine<br />
-	**[[1zpb]], [[2fda]] - hFXIa (mutant) + ketothiazole inhibitor<br />
-	**[[4na7]], [[4na8]], [[4y8x]], [[5q0d]], [[5q0e]], [[5q0g]], [[5q0h]], [[5qck]], [[5qqp]], [[5qtt]], [[5qtu]], [[5qtv]], [[5qtw]], [[5qtx]], [[5qty]] - hFXIa + inhibitor<br />
-	**[[4y8z]], [[5qcl]], [[5qcm]], [[5qcn]], [[6vlu]] - hFXIa + quinoline inhibitor<br />
-	**[[5e2o]], [[5exm]], [[5tks]], [[5tkt]], [[5wb6]], [[6ts4]], [[6ts5]], [[6ts6]], [[6usy]], [[7v0z]], [[7v10]], [[7v11]], [[7v12]], [[7v13]], [[7v14]], [[7v15]], [[7v16]], [[7v17]], [[7v18]] - hFXIa (mutant) + inhibitor<br />
-	**[[4cr5]], [[4cr9]], [[4cra]], [[4crb]], [[4cre]], [[4crf]], [[1ztl]], [[4ty7]], [[4wxi]], [[4d76]], [[4d7f]], [[4d7g]], [[5e2p]], [[6ts7]], [[6vlv]] - hFXIa (mutant) + quinolin inhibitor<br />
-	**[[4y8y]] - hFXIa + tetrazol inhibitor<br />
-	**[[4crc]], [[4crd]], [[3sor]], [[1zpc]], [[3sos]], [[4x6o]], [[5exn]], [[5tku]], [[6c0s]] - hFXIa (mutant) + tetrazol inhibitor<br />
-	**[[6w50]] - hFXIa + pyrimidine inhibitor<br />
-	**[[1ztk]], [[1ztj]], [[1zsl]], [[4crg]], [[7mbo]] - hFXIa (mutant) + pyrimidine inhibitor<br />
-	**[[4x6m]], [[4x6p]], [[5exl]] - hFXIa (mutant) + indazole inhibitor<br />
-	**[[4x6n]] - hFXIa (mutant) + indazole inhibitor + peptide<br />
-	**[[1zhm]], [[1zhp]], [[1zhr]] - hFXIa (mutant) + benzamidine inhibitor<br />
-	**[[1zrk]], [[1zsk]], [[1zsj]] - hFXIa (mutant) + naphthamidine inhibitor<br />
-	**[[1zpz]], [[1zom]] - hFXIa (mutant) + peptidomimetic inhibitor<br />
-	**[[1zmn]], [[1zml]], [[1zmj]], [[1zlr]] - hFXIa (mutant) + aryl boronic acid inhibitor<br />
-	**[[1zjd]] - hFXIa (mutant) + Kunitz protease inhibitory domain<br />
-	**[[1xx9]] - hFXIa + ecotin (mutant)<br />
-	**[[1xxd]], [[1xxf]] - hFXIa (mutant) + ecotin (mutant)<br />
-	**[[4ty6]] - hFXIa light chain (mutant) + heavy chain peptide + benzamine inhibitor<br />
-	**[[6r8x]] - hFXIa light chain + antibody<br />
-	**[[6aod]], [[6hhc]] - hFXIa light chain (mutant) + antibody<br />
-	**[[6twb]], [[6twc]] - hFXIa light chain + peptide<br />
-	**[[5q0f]], [[5qqo]] - hFXIa light chain + peptide + inhibitor<br />
-	**[[7qot]] - hFXIa heavy chain + kiniogen<br />
-	}}
	==References==		==References==
	<references />		<references />

	[[Category:Topic Page]]		[[Category:Topic Page]]

Michal Harel at 10:03, 27 February 2023

2023-02-27T10:03:30Z

←Older revision		Revision as of 10:03, 27 February 2023
Line 2:		Line 2:
	[[Image:Coag_cartoon.jpg \|left\| thumb \|300px\| Schematic representation of the coagulation response]]		[[Image:Coag_cartoon.jpg \|left\| thumb \|300px\| Schematic representation of the coagulation response]]
	{{Clear}}		{{Clear}}
		+	__TOC__
	==Coagulation Factor XIa==		==Coagulation Factor XIa==
	===Introduction===		===Introduction===
Line 83:		Line 84:

	Amino acid substitutions such as Phe283Leu<ref>PMID:17257616</ref> and Gly350Glu<ref>PMID:15026311 </ref> in the heavy chain results in an increased dimer dissociation and absence of dimer formation respectively. Some mutations in the factor XI A4 domain and catalytic domains are inherited as autosomal recessive bleeding diathesis however, other amino acid substitutions are exert a dominant negative effect on the normal monomer subunit affecting protein secretion. Studies suggest that dimerization is not affected under dominant negative mutations but the mutant subunit traps the normal subunit in the cell preventing its secretion. Majority of these missense mutations:Ser225Phe, Cys398Tyr, Gly400Val and Trp569Ser which produce a dominant negative effect involves residues found in the catalytic domain<ref>PMID:15026311 </ref>.		Amino acid substitutions such as Phe283Leu<ref>PMID:17257616</ref> and Gly350Glu<ref>PMID:15026311 </ref> in the heavy chain results in an increased dimer dissociation and absence of dimer formation respectively. Some mutations in the factor XI A4 domain and catalytic domains are inherited as autosomal recessive bleeding diathesis however, other amino acid substitutions are exert a dominant negative effect on the normal monomer subunit affecting protein secretion. Studies suggest that dimerization is not affected under dominant negative mutations but the mutant subunit traps the normal subunit in the cell preventing its secretion. Majority of these missense mutations:Ser225Phe, Cys398Tyr, Gly400Val and Trp569Ser which produce a dominant negative effect involves residues found in the catalytic domain<ref>PMID:15026311 </ref>.
		+	==3D structures of Factor XIa==
		+	[[Factor XIa 3D structures]]
	</StructureSection>		</StructureSection>
-	~~__NOTOC__~~	+

	==3D structures of Factor XIa==		==3D structures of Factor XIa==
Line 99:		Line 102:
	**[[3bg8]] – hFXIa + clavatadine<br />		**[[3bg8]] – hFXIa + clavatadine<br />
	**[[1zpb]], [[2fda]] - hFXIa (mutant) + ketothiazole inhibitor<br />		**[[1zpb]], [[2fda]] - hFXIa (mutant) + ketothiazole inhibitor<br />
-	**[[4na7]], [[4na8]], [[4y8x]], [[~~6usy~~]] - hFXIa + inhibitor<br />	+	**[[4na7]], [[4na8]], [[4y8x]], [[5q0d]], [[5q0e]], [[5q0g]], [[5q0h]], [[5qck]], [[5qqp]], [[5qtt]], [[5qtu]], [[5qtv]], [[5qtw]], [[5qtx]], [[5qty]] - hFXIa + inhibitor<br />
-	**[[4y8z]], [[6vlu]] - hFXIa + quinoline inhibitor<br />	+	**[[4y8z]], [[5qcl]], [[5qcm]], [[5qcn]], [[6vlu]] - hFXIa + quinoline inhibitor<br />
-	**[[5e2o]], [[5exm]], [[5tkt]], [[6ts4]], [[6ts5]], [[6ts6]] - hFXIa (mutant) + inhibitor<br />	+	**[[5e2o]], [[5exm]], [[5tks]], [[5tkt]], [[5wb6]], [[6ts4]], [[6ts5]], [[6ts6]], [[6usy]], [[7v0z]], [[7v10]], [[7v11]], [[7v12]], [[7v13]], [[7v14]], [[7v15]], [[7v16]], [[7v17]], [[7v18]] - hFXIa (mutant) + inhibitor<br />
	**[[4cr5]], [[4cr9]], [[4cra]], [[4crb]], [[4cre]], [[4crf]], [[1ztl]], [[4ty7]], [[4wxi]], [[4d76]], [[4d7f]], [[4d7g]], [[5e2p]], [[6ts7]], [[6vlv]] - hFXIa (mutant) + quinolin inhibitor<br />		**[[4cr5]], [[4cr9]], [[4cra]], [[4crb]], [[4cre]], [[4crf]], [[1ztl]], [[4ty7]], [[4wxi]], [[4d76]], [[4d7f]], [[4d7g]], [[5e2p]], [[6ts7]], [[6vlv]] - hFXIa (mutant) + quinolin inhibitor<br />
	**[[4y8y]] - hFXIa + tetrazol inhibitor<br />		**[[4y8y]] - hFXIa + tetrazol inhibitor<br />
	**[[4crc]], [[4crd]], [[3sor]], [[1zpc]], [[3sos]], [[4x6o]], [[5exn]], [[5tku]], [[6c0s]] - hFXIa (mutant) + tetrazol inhibitor<br />		**[[4crc]], [[4crd]], [[3sor]], [[1zpc]], [[3sos]], [[4x6o]], [[5exn]], [[5tku]], [[6c0s]] - hFXIa (mutant) + tetrazol inhibitor<br />
	**[[6w50]] - hFXIa + pyrimidine inhibitor<br />		**[[6w50]] - hFXIa + pyrimidine inhibitor<br />
-	**[[1ztk]], [[1ztj]], [[1zsl]], [[4crg]] - hFXIa (mutant) + pyrimidine inhibitor<br />	+	**[[1ztk]], [[1ztj]], [[1zsl]], [[4crg]], [[7mbo]] - hFXIa (mutant) + pyrimidine inhibitor<br />
	**[[4x6m]], [[4x6p]], [[5exl]] - hFXIa (mutant) + indazole inhibitor<br />		**[[4x6m]], [[4x6p]], [[5exl]] - hFXIa (mutant) + indazole inhibitor<br />
	**[[4x6n]] - hFXIa (mutant) + indazole inhibitor + peptide<br />		**[[4x6n]] - hFXIa (mutant) + indazole inhibitor + peptide<br />
Line 120:		Line 123:
	**[[6aod]], [[6hhc]] - hFXIa light chain (mutant) + antibody<br />		**[[6aod]], [[6hhc]] - hFXIa light chain (mutant) + antibody<br />
	**[[6twb]], [[6twc]] - hFXIa light chain + peptide<br />		**[[6twb]], [[6twc]] - hFXIa light chain + peptide<br />
		+	**[[5q0f]], [[5qqo]] - hFXIa light chain + peptide + inhibitor<br />
		+	**[[7qot]] - hFXIa heavy chain + kiniogen<br />
	}}		}}
	==References==		==References==

Michal Harel at 09:11, 22 July 2021

2021-07-22T09:11:46Z

←Older revision		Revision as of 09:11, 22 July 2021
Line 93:		Line 93:
	*Factor XIa		*Factor XIa
	**[[2j8j]], [[2j8l]] – hFXIa A4 domain (residues 290-379) – human – NMR<br />		**[[2j8j]], [[2j8l]] – hFXIa A4 domain (residues 290-379) – human – NMR<br />
-	**[[2f83]] - hFXIa zymogen (residues 1-625)	+	**[[2f83]], [[6i58]] - hFXIa zymogen (residues 1-625)

	*Factor XIa light chain catalytic domain (residues 388-625) inhibitor complex		*Factor XIa light chain catalytic domain (residues 388-625) inhibitor complex
Line 101:		Line 101:
	**[[4na7]], [[4na8]], [[4y8x]], [[6usy]] - hFXIa + inhibitor<br />		**[[4na7]], [[4na8]], [[4y8x]], [[6usy]] - hFXIa + inhibitor<br />
	**[[4y8z]], [[6vlu]] - hFXIa + quinoline inhibitor<br />		**[[4y8z]], [[6vlu]] - hFXIa + quinoline inhibitor<br />
-	**[[5e2o]], [[5exm]], [[5tkt]] - hFXIa (mutant) + inhibitor<br />	+	**[[5e2o]], [[5exm]], [[5tkt]], [[6ts4]], [[6ts5]], [[6ts6]] - hFXIa (mutant) + inhibitor<br />
-	**[[4cr5]], [[4cr9]], [[4cra]], [[4crb]], [[4cre]], [[4crf]], [[1ztl]], [[4ty7]], [[4wxi]], [[4d76]], [[4d7f]], [[4d7g]], [[5e2p]], [[6vlv]] - hFXIa (mutant) + quinolin inhibitor<br />	+	**[[4cr5]], [[4cr9]], [[4cra]], [[4crb]], [[4cre]], [[4crf]], [[1ztl]], [[4ty7]], [[4wxi]], [[4d76]], [[4d7f]], [[4d7g]], [[5e2p]], [[6ts7]], [[6vlv]] - hFXIa (mutant) + quinolin inhibitor<br />
	**[[4y8y]] - hFXIa + tetrazol inhibitor<br />		**[[4y8y]] - hFXIa + tetrazol inhibitor<br />
-	**[[4crc]], [[4crd]], [[3sor]], [[1zpc]], [[3sos]], [[4x6o]], [[5exn]], [[5tku]] - hFXIa (mutant) + tetrazol inhibitor<br />	+	**[[4crc]], [[4crd]], [[3sor]], [[1zpc]], [[3sos]], [[4x6o]], [[5exn]], [[5tku]], [[6c0s]] - hFXIa (mutant) + tetrazol inhibitor<br />
-	**[[~~4crg~~]] - hFXIa ~~(mutant)~~ + pyrimidine inhibitor<br />	+	**[[6w50]] - hFXIa + pyrimidine inhibitor<br />
-	**[[1ztk]], [[1ztj]], [[1zsl]] - hFXIa (mutant) + ~~pyrimidinone~~ inhibitor<br />	+	**[[1ztk]], [[1ztj]], [[1zsl]], [[4crg]] - hFXIa (mutant) + pyrimidine inhibitor<br />
	**[[4x6m]], [[4x6p]], [[5exl]] - hFXIa (mutant) + indazole inhibitor<br />		**[[4x6m]], [[4x6p]], [[5exl]] - hFXIa (mutant) + indazole inhibitor<br />
	**[[4x6n]] - hFXIa (mutant) + indazole inhibitor + peptide<br />		**[[4x6n]] - hFXIa (mutant) + indazole inhibitor + peptide<br />
Line 117:		Line 117:
	**[[1xxd]], [[1xxf]] - hFXIa (mutant) + ecotin (mutant)<br />		**[[1xxd]], [[1xxf]] - hFXIa (mutant) + ecotin (mutant)<br />
	**[[4ty6]] - hFXIa light chain (mutant) + heavy chain peptide + benzamine inhibitor<br />		**[[4ty6]] - hFXIa light chain (mutant) + heavy chain peptide + benzamine inhibitor<br />
		+	**[[6r8x]] - hFXIa light chain + antibody<br />
		+	**[[6aod]], [[6hhc]] - hFXIa light chain (mutant) + antibody<br />
		+	**[[6twb]], [[6twc]] - hFXIa light chain + peptide<br />
	}}		}}
	==References==		==References==

Michal Harel at 09:31, 26 July 2020

2020-07-26T09:31:18Z

←Older revision		Revision as of 09:31, 26 July 2020
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	**[[3bg8]] – hFXIa + clavatadine<br />		**[[3bg8]] – hFXIa + clavatadine<br />
	**[[1zpb]], [[2fda]] - hFXIa (mutant) + ketothiazole inhibitor<br />		**[[1zpb]], [[2fda]] - hFXIa (mutant) + ketothiazole inhibitor<br />
-	**[[4na7]], [[4na8]], [[4y8x]] - hFXIa + inhibitor<br />	+	**[[4na7]], [[4na8]], [[4y8x]], [[6usy]] - hFXIa + inhibitor<br />
-	**[[4y8z]] - hFXIa + quinoline inhibitor<br />	+	**[[4y8z]], [[6vlu]] - hFXIa + quinoline inhibitor<br />
	**[[5e2o]], [[5exm]], [[5tkt]] - hFXIa (mutant) + inhibitor<br />		**[[5e2o]], [[5exm]], [[5tkt]] - hFXIa (mutant) + inhibitor<br />
-	**[[4cr5]], [[4cr9]], [[4cra]], [[4crb]], [[4cre]], [[4crf]], [[1ztl]], [[4ty7]], [[4wxi]], [[4d76]], [[4d7f]], [[4d7g]], [[5e2p]] - hFXIa (mutant) + quinolin inhibitor<br />	+	**[[4cr5]], [[4cr9]], [[4cra]], [[4crb]], [[4cre]], [[4crf]], [[1ztl]], [[4ty7]], [[4wxi]], [[4d76]], [[4d7f]], [[4d7g]], [[5e2p]], [[6vlv]] - hFXIa (mutant) + quinolin inhibitor<br />
	**[[4y8y]] - hFXIa + tetrazol inhibitor<br />		**[[4y8y]] - hFXIa + tetrazol inhibitor<br />
	**[[4crc]], [[4crd]], [[3sor]], [[1zpc]], [[3sos]], [[4x6o]], [[5exn]], [[5tku]] - hFXIa (mutant) + tetrazol inhibitor<br />		**[[4crc]], [[4crd]], [[3sor]], [[1zpc]], [[3sos]], [[4x6o]], [[5exn]], [[5tku]] - hFXIa (mutant) + tetrazol inhibitor<br />

Michal Harel at 06:46, 23 May 2018

2018-05-23T06:46:33Z

←Older revision		Revision as of 06:46, 23 May 2018
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	<StructureSection load='1zmn' size='350' side='right' scene='' caption='Human factor XIa catalytic domain complex with aryl boronic acid derivative and sulfate (PDB code [[1zmn]])'>		<StructureSection load='1zmn' size='350' side='right' scene='' caption='Human factor XIa catalytic domain complex with aryl boronic acid derivative and sulfate (PDB code [[1zmn]])'>
-	[[Image:Coag_cartoon.jpg \|left\| thumb \|~~200px~~\| Schematic representation of the coagulation response]]	+	[[Image:Coag_cartoon.jpg \|left\| thumb \|300px\| Schematic representation of the coagulation response]]
	{{Clear}}		{{Clear}}
	==Coagulation Factor XIa==		==Coagulation Factor XIa==

Michal Harel at 06:46, 23 May 2018

2018-05-23T06:46:04Z

←Older revision		Revision as of 06:46, 23 May 2018
Line 1:		Line 1:
	<StructureSection load='1zmn' size='350' side='right' scene='' caption='Human factor XIa catalytic domain complex with aryl boronic acid derivative and sulfate (PDB code [[1zmn]])'>		<StructureSection load='1zmn' size='350' side='right' scene='' caption='Human factor XIa catalytic domain complex with aryl boronic acid derivative and sulfate (PDB code [[1zmn]])'>
-	[[Image:Coag_cartoon.jpg \|left\| thumb \|~~450px~~\| Schematic representation of the coagulation response]]	+	[[Image:Coag_cartoon.jpg \|left\| thumb \|200px\| Schematic representation of the coagulation response]]
	{{Clear}}		{{Clear}}
	==Coagulation Factor XIa==		==Coagulation Factor XIa==

Michal Harel at 09:30, 22 May 2018

2018-05-22T09:30:48Z

←Older revision		Revision as of 09:30, 22 May 2018
Line 102:		Line 102:
	**[[4y8z]] - hFXIa + quinoline inhibitor<br />		**[[4y8z]] - hFXIa + quinoline inhibitor<br />
	**[[5e2o]], [[5exm]], [[5tkt]] - hFXIa (mutant) + inhibitor<br />		**[[5e2o]], [[5exm]], [[5tkt]] - hFXIa (mutant) + inhibitor<br />
-	**[[4cr5]], [[4cr9]], [[4cra]], [[4crb]], [[4cre]], [[4crf]], [[1ztl]], [[4ty7]], [[4wxi]], [[4d7g]], [[5e2p]] - hFXIa (mutant) + quinolin inhibitor<br />	+	**[[4cr5]], [[4cr9]], [[4cra]], [[4crb]], [[4cre]], [[4crf]], [[1ztl]], [[4ty7]], [[4wxi]], [[4d76]], [[4d7f]], [[4d7g]], [[5e2p]] - hFXIa (mutant) + quinolin inhibitor<br />
	**[[4y8y]] - hFXIa + tetrazol inhibitor<br />		**[[4y8y]] - hFXIa + tetrazol inhibitor<br />
	**[[4crc]], [[4crd]], [[3sor]], [[1zpc]], [[3sos]], [[4x6o]], [[5exn]], [[5tku]] - hFXIa (mutant) + tetrazol inhibitor<br />		**[[4crc]], [[4crd]], [[3sor]], [[1zpc]], [[3sos]], [[4x6o]], [[5exn]], [[5tku]] - hFXIa (mutant) + tetrazol inhibitor<br />

Michal Harel at 10:08, 11 May 2017

2017-05-11T10:08:51Z

←Older revision		Revision as of 10:08, 11 May 2017
Line 6:		Line 6:
	'''Factor XIa''' is unique protease derived from the activation of the coagulation zymogen, factor XI. Factor XIa partcipates in the procoagulant response via contact activation pathway. Synthesized by the liver similar to most vitamin K-dependent coagulation proteins, the zymogen, factor XI circulates in plasma as a 160 kDa disulfide-linked homodimer in complex with high molecular weight kininogen (HK)<ref>PMID:915004</ref>. Studies show that factor XI is a substrate for various plasma proteins such as factor XIIa, thrombin, meizothrombin and factor XIa (via autoactivation). Proteolysis of the <scene name='Sandbox/Arg369-ile370/1'> Arg369-Ile370</scene> bond generates the active enzyme factor XIa which in turn cleaves its substrate factor IX to produce the serine protease factor IXa.		'''Factor XIa''' is unique protease derived from the activation of the coagulation zymogen, factor XI. Factor XIa partcipates in the procoagulant response via contact activation pathway. Synthesized by the liver similar to most vitamin K-dependent coagulation proteins, the zymogen, factor XI circulates in plasma as a 160 kDa disulfide-linked homodimer in complex with high molecular weight kininogen (HK)<ref>PMID:915004</ref>. Studies show that factor XI is a substrate for various plasma proteins such as factor XIIa, thrombin, meizothrombin and factor XIa (via autoactivation). Proteolysis of the <scene name='Sandbox/Arg369-ile370/1'> Arg369-Ile370</scene> bond generates the active enzyme factor XIa which in turn cleaves its substrate factor IX to produce the serine protease factor IXa.

-	==Protein Structure==	+	===Protein Structure===
	'''Factor XIa''' is a <scene name='Sandbox/Disulfides/1'>disulfide</scene> linked-dimer of similar amino acid composition of approximately 625 residues. The first 18 amino acid residues constitute the signal peptide whereas residues 19-387 and 388-625 represents the heavy- and light- chains of the factor XIa molecule respectively. The protein forms five main distinct domains. Beginning from the N-terminus,each dimeric subunit contains 4 apple domains (<scene name='Sandbox/A1_domain/1'>A1</scene>, <scene name='Sandbox/A2_domain/1'>A2</scene>, <scene name='Sandbox/A3_domain/1'>A3</scene> and <scene name='Sandbox/A4_domain/2'>A4</scene>) which are characterized by approximately 90 or 91 amino acid residues. Protein-protein interactions are thought to be the primary role of the apple domains. The <scene name='Sandbox/A3_domain/1'>A3 domain</scene> is reported to mediate binding to platelet glycoprotein Ib (GPIb)<ref>PMID:15317813</ref> as well as interactions with exosite I of thrombin, and kringle 2 domain of prothrombin. The <scene name='Sandbox/A1_domain/1'>A1 domain</scene> is the main site of factor XI protein-protein interaction when in complex with high molecular weight kininogen<ref>PMID:7686159</ref>. The C-terminus (heavy chain) of factor XIa contain a trypsin-like catalytic domain <ref>PMID:893417</ref>. Together with Prekallikrein (PK) a monomeric homolog of factor XIa, they belong to the PAN (plasminogen, apple, nematode) module family which all have a conserved N-terminal apple domain found in hepatocyte growth factor and plasminogen <ref>PMID:10561497</ref>.		'''Factor XIa''' is a <scene name='Sandbox/Disulfides/1'>disulfide</scene> linked-dimer of similar amino acid composition of approximately 625 residues. The first 18 amino acid residues constitute the signal peptide whereas residues 19-387 and 388-625 represents the heavy- and light- chains of the factor XIa molecule respectively. The protein forms five main distinct domains. Beginning from the N-terminus,each dimeric subunit contains 4 apple domains (<scene name='Sandbox/A1_domain/1'>A1</scene>, <scene name='Sandbox/A2_domain/1'>A2</scene>, <scene name='Sandbox/A3_domain/1'>A3</scene> and <scene name='Sandbox/A4_domain/2'>A4</scene>) which are characterized by approximately 90 or 91 amino acid residues. Protein-protein interactions are thought to be the primary role of the apple domains. The <scene name='Sandbox/A3_domain/1'>A3 domain</scene> is reported to mediate binding to platelet glycoprotein Ib (GPIb)<ref>PMID:15317813</ref> as well as interactions with exosite I of thrombin, and kringle 2 domain of prothrombin. The <scene name='Sandbox/A1_domain/1'>A1 domain</scene> is the main site of factor XI protein-protein interaction when in complex with high molecular weight kininogen<ref>PMID:7686159</ref>. The C-terminus (heavy chain) of factor XIa contain a trypsin-like catalytic domain <ref>PMID:893417</ref>. Together with Prekallikrein (PK) a monomeric homolog of factor XIa, they belong to the PAN (plasminogen, apple, nematode) module family which all have a conserved N-terminal apple domain found in hepatocyte growth factor and plasminogen <ref>PMID:10561497</ref>.

Line 93:		Line 93:
	*Factor XIa		*Factor XIa
	**[[2j8j]], [[2j8l]] – hFXIa A4 domain (residues 290-379) – human – NMR<br />		**[[2j8j]], [[2j8l]] – hFXIa A4 domain (residues 290-379) – human – NMR<br />
-	**[[2f83]] - ~~hFXI~~ zymogen (residues 1-625)	+	**[[2f83]] - hFXIa zymogen (residues 1-625)

	*Factor XIa light chain catalytic domain (residues 388-625) inhibitor complex		*Factor XIa light chain catalytic domain (residues 388-625) inhibitor complex

	**[[3bg8]] – hFXIa + clavatadine<br />		**[[3bg8]] – hFXIa + clavatadine<br />
-	**[[1zpb]], [[2fda]] - ~~hFXI~~ (mutant) + ketothiazole inhibitor<br />	+	**[[1zpb]], [[2fda]] - hFXIa (mutant) + ketothiazole inhibitor<br />
-	**[[4na7]], [[4na8]] - ~~hFXI~~ + inhibitor<br />	+	**[[4na7]], [[4na8]], [[4y8x]] - hFXIa + inhibitor<br />
-	**[[4cr5]], [[4cr9]], [[4cra]], [[4crb]], [[4cre]], [[4crf]], [[1ztl]], [[4ty7]], [[4wxi]] - ~~hFXI~~ (mutant) + quinolin inhibitor<br />	+	**[[4y8z]] - hFXIa + quinoline inhibitor<br />
-	**[[4crc]], [[4crd]], [[3sor]], [[1zpc]], [[3sos]], [[4x6o]] - ~~hFXI~~ (mutant) + tetrazol inhibitor<br />	+	**[[5e2o]], [[5exm]], [[5tkt]] - hFXIa (mutant) + inhibitor<br />
-	**[[4crg]] - ~~hFXI~~ (mutant) + pyrimidine inhibitor<br />	+	**[[4cr5]], [[4cr9]], [[4cra]], [[4crb]], [[4cre]], [[4crf]], [[1ztl]], [[4ty7]], [[4wxi]], [[4d7g]], [[5e2p]] - hFXIa (mutant) + quinolin inhibitor<br />
-	**[[1ztk]], [[1ztj]], [[1zsl]] - ~~hFXI~~ (mutant) + pyrimidinone inhibitor<br />	+	**[[4y8y]] - hFXIa + tetrazol inhibitor<br />
-	**[[4x6m]], [[4x6p]] - ~~hFXI~~ (mutant) + indazole inhibitor<br />	+	**[[4crc]], [[4crd]], [[3sor]], [[1zpc]], [[3sos]], [[4x6o]], [[5exn]], [[5tku]] - hFXIa (mutant) + tetrazol inhibitor<br />
-	**[[4x6n]] - ~~hFXI~~ (mutant) + indazole inhibitor + peptide<br />	+	**[[4crg]] - hFXIa (mutant) + pyrimidine inhibitor<br />
-	**[[1zhm]], [[1zhp]], [[1zhr]] - ~~hFXI~~ (mutant) + benzamidine inhibitor<br />	+	**[[1ztk]], [[1ztj]], [[1zsl]] - hFXIa (mutant) + pyrimidinone inhibitor<br />
-	**[[1zrk]], [[1zsk]], [[1zsj]] - ~~hFXI~~ (mutant) + naphthamidine inhibitor<br />	+	**[[4x6m]], [[4x6p]], [[5exl]] - hFXIa (mutant) + indazole inhibitor<br />
-	**[[1zpz]], [[1zom]] - ~~hFXI~~ (mutant) + peptidomimetic inhibitor<br />	+	**[[4x6n]] - hFXIa (mutant) + indazole inhibitor + peptide<br />
-	**[[1zmn]], [[1zml]], [[1zmj]], [[1zlr]] - ~~hFXI~~ (mutant) + aryl boronic acid inhibitor<br />	+	**[[1zhm]], [[1zhp]], [[1zhr]] - hFXIa (mutant) + benzamidine inhibitor<br />
-	**[[1zjd]] - ~~hFXI~~ (mutant) + Kunitz protease inhibitory domain<br />	+	**[[1zrk]], [[1zsk]], [[1zsj]] - hFXIa (mutant) + naphthamidine inhibitor<br />
-	**[[1xx9]] - ~~hFXI~~ + ecotin (mutant)<br />	+	**[[1zpz]], [[1zom]] - hFXIa (mutant) + peptidomimetic inhibitor<br />
-	**[[1xxd]], [[1xxf]] - ~~hFXI~~ (mutant) + ecotin (mutant)<br />	+	**[[1zmn]], [[1zml]], [[1zmj]], [[1zlr]] - hFXIa (mutant) + aryl boronic acid inhibitor<br />
-	**[[4ty6]] - ~~hFXI~~ light chain (mutant) + heavy chain peptide + benzamine inhibitor<br />	+	**[[1zjd]] - hFXIa (mutant) + Kunitz protease inhibitory domain<br />
		+	**[[1xx9]] - hFXIa + ecotin (mutant)<br />
		+	**[[1xxd]], [[1xxf]] - hFXIa (mutant) + ecotin (mutant)<br />
		+	**[[4ty6]] - hFXIa light chain (mutant) + heavy chain peptide + benzamine inhibitor<br />
	}}		}}
	==References==		==References==

Michal Harel at 20:41, 20 January 2016

2016-01-20T20:41:41Z

←Older revision		Revision as of 20:41, 20 January 2016
Line 1:		Line 1:
-	<StructureSection load='1zmn' size='~~450~~' side='right' scene='' caption='Human factor XIa catalytic domain complex with aryl boronic acid derivative and sulfate (PDB code [[1zmn]])'>	+	<StructureSection load='1zmn' size='350' side='right' scene='' caption='Human factor XIa catalytic domain complex with aryl boronic acid derivative and sulfate (PDB code [[1zmn]])'>
	[[Image:Coag_cartoon.jpg \|left\| thumb \|450px\| Schematic representation of the coagulation response]]		[[Image:Coag_cartoon.jpg \|left\| thumb \|450px\| Schematic representation of the coagulation response]]
	{{Clear}}		{{Clear}}

Michal Harel at 10:53, 1 April 2015

2015-04-01T10:53:34Z

←Older revision		Revision as of 10:53, 1 April 2015
Line 98:		Line 98:

	**[[3bg8]] – hFXIa + clavatadine<br />		**[[3bg8]] – hFXIa + clavatadine<br />
-	**[[1zpb[[, [[2fda]] - hFXI (mutant) + ketothiazole inhibitor<br />	+	**[[1zpb]], [[2fda]] - hFXI (mutant) + ketothiazole inhibitor<br />
	**[[4na7]], [[4na8]] - hFXI + inhibitor<br />		**[[4na7]], [[4na8]] - hFXI + inhibitor<br />
	**[[4cr5]], [[4cr9]], [[4cra]], [[4crb]], [[4cre]], [[4crf]], [[1ztl]], [[4ty7]], [[4wxi]] - hFXI (mutant) + quinolin inhibitor<br />		**[[4cr5]], [[4cr9]], [[4cra]], [[4crb]], [[4cre]], [[4crf]], [[1ztl]], [[4ty7]], [[4wxi]] - hFXI (mutant) + quinolin inhibitor<br />