3f6u - Revision history

OCA at 14:05, 13 March 2024

2024-03-13T14:05:13Z

←Older revision		Revision as of 14:05, 13 March 2024
Line 22:		Line 22:
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3f6u ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3f6u ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	The serine protease domain of activated protein C (APC) contains a Na+ and a Ca2+ site. However, the number and identity of the APC residues that coordinate to Na+ is not precisely known. Further, the functional link between the Na+ and the Ca2+ site is insufficiently defined, and their linkage to the substrate S1 site has not been studied. Here, we systematically investigate the functional significance of these two cation sites and their thermodynamic links to the S1 site. Kinetic data reveal that Na+ binds to the substrate-occupied APC with K(d) values of approximately 24 mm in the absence and approximately 6 mm in the presence of Ca2+. Sodium-occupied APC has approximately 100-fold increased catalytic efficiency ( approximately 4-fold decrease in K(m) and approximately 25-fold increase in k(cat)) in hydrolyzing S-2288 (H-d-Ile-Pro-Arg-p-nitroanilide) and Ca2+ further increases this k(cat) slightly ( approximately 1.2-fold). Ca2+ binds to the protease domain of APC with K(d) values of approximately 438 microm in the absence and approximately 105 microm in the presence of Na+. Ca2+ binding to the protease domain of APC does not affect K(m) but increases the k(cat) approximately 10-fold, and Na+ further increases this k(cat) approximately 3-fold and decreases the K(m) value approximately 3.7-fold. In agreement with the K(m) data, sodium-occupied APC has approximately 4-fold increased affinity in binding to p-aminobenzamidine (S1 probe). Crystallographically, the Ca2+ site in APC is similar to that in trypsin, and the Na+ site is similar to that in factor Xa but not thrombin. Collectively, the Na+ site is thermodynamically linked to the S1 site as well as to the protease domain Ca2+ site, whereas the Ca2+ site is only linked to the Na+ site. The significance of these findings is that under physiologic conditions, most of the APC will exist in Na2+-APC-Ca2+ form, which has 110-fold increased proteolytic activity.
-
-	Thermodynamic linkage between the S1 site, the Na+ site, and the Ca2+ site in the protease domain of human activated protein C (APC). Sodium ion in the APC crystal structure is coordinated to four carbonyl groups from two separate loops.,Schmidt AE, Padmanabhan K, Underwood MC, Bode W, Mather T, Bajaj SP J Biol Chem. 2002 Aug 9;277(32):28987-95. Epub 2002 May 23. PMID:12029084<ref>PMID:12029084</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 3f6u" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 06:42, 6 September 2023

2023-09-06T06:42:33Z

←Older revision		Revision as of 06:42, 6 September 2023
Line 3:		Line 3:
	<StructureSection load='3f6u' size='340' side='right'caption='[[3f6u]], [[Resolution\|resolution]] 2.80Å' scene=''>		<StructureSection load='3f6u' size='340' side='right'caption='[[3f6u]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3f6u]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3F6U OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=3F6U FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3f6u]] 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=3F6U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3F6U FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0G6:D-PHENYLALANYL-N-[(2S,3S)-6-{[AMINO(IMINIO)METHYL]AMINO}-1-CHLORO-2-HYDROXYHEXAN-3-YL]-L-PROLINAMIDE'>0G6</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 2.8Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1aut\|1aut]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0G6:D-PHENYLALANYL-N-[(2S,3S)-6-{[AMINO(IMINIO)METHYL]AMINO}-1-CHLORO-2-HYDROXYHEXAN-3-YL]-L-PROLINAMIDE'>0G6</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein_C_(activated) Protein C (activated)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.69 3.4.21.69] </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=3f6u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f6u OCA], [https://pdbe.org/3f6u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3f6u RCSB], [https://www.ebi.ac.uk/pdbsum/3f6u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3f6u 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=3f6u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f6u OCA], [~~http~~://pdbe.org/3f6u PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3f6u RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3f6u PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3f6u ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/PROC_HUMAN PROC_HUMAN]] Defects in PROC are the cause of thrombophilia due to protein C deficiency, autosomal dominant (THPH3) [MIM:[~~http~~://omim.org/entry/176860 176860]]. A hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. However, many adults with heterozygous disease may be asymptomatic. Individuals with decreased amounts of protein C are classically referred to as having type I protein C deficiency and those with normal amounts of a functionally defective protein as having type II deficiency.<ref>PMID:8560401</ref> <ref>PMID:2437584</ref> <ref>PMID:2602169</ref> <ref>PMID:1868249</ref> <ref>PMID:1347706</ref> <ref>PMID:1511989</ref> <ref>PMID:1301959</ref> <ref>PMID:8499568</ref> <ref>PMID:8292730</ref> <ref>PMID:8398832</ref> <ref>PMID:7865674</ref> <ref>PMID:7792728</ref> <ref>PMID:8829639</ref> <ref>PMID:9798967</ref> Defects in PROC are the cause of thrombophilia due to protein C deficiency, autosomal recessive (THPH4) [MIM:[~~http~~://omim.org/entry/612304 612304]]. A hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. It results in a thrombotic condition that can manifest as a severe neonatal disorder or as a milder disorder with late-onset thrombophilia. The severe form leads to neonatal death through massive neonatal venous thrombosis. Often associated with ecchymotic skin lesions which can turn necrotic called purpura fulminans, this disorder is very rare.	+	[https://www.uniprot.org/uniprot/PROC_HUMAN PROC_HUMAN] Defects in PROC are the cause of thrombophilia due to protein C deficiency, autosomal dominant (THPH3) [MIM:[https://omim.org/entry/176860 176860]. A hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. However, many adults with heterozygous disease may be asymptomatic. Individuals with decreased amounts of protein C are classically referred to as having type I protein C deficiency and those with normal amounts of a functionally defective protein as having type II deficiency.<ref>PMID:8560401</ref> <ref>PMID:2437584</ref> <ref>PMID:2602169</ref> <ref>PMID:1868249</ref> <ref>PMID:1347706</ref> <ref>PMID:1511989</ref> <ref>PMID:1301959</ref> <ref>PMID:8499568</ref> <ref>PMID:8292730</ref> <ref>PMID:8398832</ref> <ref>PMID:7865674</ref> <ref>PMID:7792728</ref> <ref>PMID:8829639</ref> <ref>PMID:9798967</ref> Defects in PROC are the cause of thrombophilia due to protein C deficiency, autosomal recessive (THPH4) [MIM:[https://omim.org/entry/612304 612304]. A hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. It results in a thrombotic condition that can manifest as a severe neonatal disorder or as a milder disorder with late-onset thrombophilia. The severe form leads to neonatal death through massive neonatal venous thrombosis. Often associated with ecchymotic skin lesions which can turn necrotic called purpura fulminans, this disorder is very rare.
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/PROC_HUMAN PROC_HUMAN]] Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids.	+	[https://www.uniprot.org/uniprot/PROC_HUMAN PROC_HUMAN] Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 25:		Line 24:
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
-	The ~~structure~~ of ~~the Gla-domainless form of the human anticoagulant enzyme~~ activated protein C ~~has been solved at 2~~.~~8 A resolution~~. ~~The light chain~~ is ~~composed~~ of two ~~domains: an epidermal growth factor~~ (~~EGF~~)-~~like domain modified by a large insert containing an additional disulfide, followed by a typical EGF~~-~~like domain~~. ~~The arrangement of~~ the ~~long axis~~ of ~~these domains describes an angle~~ of approximately ~~80 degrees~~. ~~Disulfide linked~~ to the ~~light chain is the catalytic~~ domain, ~~which is generally trypsin~~-~~like but contains a large insertion loop at~~ the ~~edge of~~ the ~~active site~~, ~~a third helical segment, a prominent cationic patch analogous~~ to ~~the anion binding exosite I of thrombin and a trypsin~~-~~like Ca[II] binding site~~. ~~The arrangement of loops around~~ the ~~active~~ site ~~partially restricts access~~ to ~~the cleft. The S2~~ and ~~S4 subsites are much more polar than~~ in factor Xa ~~and~~ thrombin, ~~and~~ the S2 site is ~~unrestricted. While quite open and exposed,~~ the ~~active~~ site ~~contains a prominent groove~~, the ~~surface of which~~ is ~~very polar with evidence for binding sites on~~ the ~~primed side~~, ~~in addition to those typical~~ of the ~~trypsin class found on the non~~-~~primed side~~.	+	The serine protease domain of activated protein C (APC) contains a Na+ and a Ca2+ site. However, the number and identity of the APC residues that coordinate to Na+ is not precisely known. Further, the functional link between the Na+ and the Ca2+ site is insufficiently defined, and their linkage to the substrate S1 site has not been studied. Here, we systematically investigate the functional significance of these two cation sites and their thermodynamic links to the S1 site. Kinetic data reveal that Na+ binds to the substrate-occupied APC with K(d) values of approximately 24 mm in the absence and approximately 6 mm in the presence of Ca2+. Sodium-occupied APC has approximately 100-fold increased catalytic efficiency ( approximately 4-fold decrease in K(m) and approximately 25-fold increase in k(cat)) in hydrolyzing S-2288 (H-d-Ile-Pro-Arg-p-nitroanilide) and Ca2+ further increases this k(cat) slightly ( approximately 1.2-fold). Ca2+ binds to the protease domain of APC with K(d) values of approximately 438 microm in the absence and approximately 105 microm in the presence of Na+. Ca2+ binding to the protease domain of APC does not affect K(m) but increases the k(cat) approximately 10-fold, and Na+ further increases this k(cat) approximately 3-fold and decreases the K(m) value approximately 3.7-fold. In agreement with the K(m) data, sodium-occupied APC has approximately 4-fold increased affinity in binding to p-aminobenzamidine (S1 probe). Crystallographically, the Ca2+ site in APC is similar to that in trypsin, and the Na+ site is similar to that in factor Xa but not thrombin. Collectively, the Na+ site is thermodynamically linked to the S1 site as well as to the protease domain Ca2+ site, whereas the Ca2+ site is only linked to the Na+ site. The significance of these findings is that under physiologic conditions, most of the APC will exist in Na2+-APC-Ca2+ form, which has 110-fold increased proteolytic activity.

-	~~The 2.8 A crystal structure~~ of ~~Gla-domainless~~ activated protein C.,~~Mather T~~, ~~Oganessyan V~~, ~~Hof P, Huber R, Foundling S, Esmon C~~, Bode W ~~EMBO~~ J. ~~1996 Dec 16~~;15(24):~~6822~~-31. PMID:~~9003757~~<ref>PMID:~~9003757~~</ref>	+	Thermodynamic linkage between the S1 site, the Na+ site, and the Ca2+ site in the protease domain of human activated protein C (APC). Sodium ion in the APC crystal structure is coordinated to four carbonyl groups from two separate loops.,Schmidt AE, Padmanabhan K, Underwood MC, Bode W, Mather T, Bajaj SP J Biol Chem. 2002 Aug 9;277(32):28987-95. Epub 2002 May 23. PMID:12029084<ref>PMID:12029084</ref>

	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
Line 38:		Line 37:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Bajaj~~, S P~~]]	+	[[Category: Bajaj SP]]
-	[[Category: Bode, W]]	+	[[Category: Bode W]]
-	[[Category: Mather, T]]	+	[[Category: Mather T]]
-	[[Category: Padmanabhan, K]]	+	[[Category: Padmanabhan K]]
-	[[Category: Schmidt~~, A E~~]]	+	[[Category: Schmidt AE]]
-	[[Category: Underwood~~, M C]]~~	+	[[Category: Underwood MC]]
-	~~[[Category: Blood coagulation]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Serine protease~~]]	+

OCA at 10:28, 9 September 2020

2020-09-09T10:28:28Z

←Older revision		Revision as of 10:28, 9 September 2020
Line 1:		Line 1:

	==Crystal structure of human Activated Protein C (APC) complexed with PPACK==		==Crystal structure of human Activated Protein C (APC) complexed with PPACK==
-	<StructureSection load='3f6u' size='340' side='right' caption='[[3f6u]], [[Resolution\|resolution]] 2.80Å' scene=''>	+	<StructureSection load='3f6u' size='340' side='right'caption='[[3f6u]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3f6u]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3F6U OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3F6U FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3f6u]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3F6U OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=3F6U FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0G6:D-PHENYLALANYL-N-[(2S,3S)-6-{[AMINO(IMINIO)METHYL]AMINO}-1-CHLORO-2-HYDROXYHEXAN-3-YL]-L-PROLINAMIDE'>0G6</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0G6:D-PHENYLALANYL-N-[(2S,3S)-6-{[AMINO(IMINIO)METHYL]AMINO}-1-CHLORO-2-HYDROXYHEXAN-3-YL]-L-PROLINAMIDE'>0G6</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1aut\|1aut]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1aut\|1aut]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein_C_(activated) Protein C (activated)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.69 3.4.21.69] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein_C_(activated) Protein C (activated)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.69 3.4.21.69] </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=3f6u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f6u OCA], [http://pdbe.org/3f6u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3f6u RCSB], [http://www.ebi.ac.uk/pdbsum/3f6u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3f6u 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=3f6u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f6u OCA], [http://pdbe.org/3f6u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3f6u RCSB], [http://www.ebi.ac.uk/pdbsum/3f6u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3f6u ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 37:		Line 37:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
	[[Category: Bajaj, S P]]		[[Category: Bajaj, S P]]
	[[Category: Bode, W]]		[[Category: Bode, W]]

OCA at 07:16, 5 December 2018

2018-12-05T07:16:03Z

←Older revision		Revision as of 07:16, 5 December 2018
Line 1:		Line 1:
		+
	==Crystal structure of human Activated Protein C (APC) complexed with PPACK==		==Crystal structure of human Activated Protein C (APC) complexed with PPACK==
	<StructureSection load='3f6u' size='340' side='right' caption='[[3f6u]], [[Resolution\|resolution]] 2.80Å' scene=''>		<StructureSection load='3f6u' size='340' side='right' caption='[[3f6u]], [[Resolution\|resolution]] 2.80Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1aut\|1aut]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1aut\|1aut]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein_C_(activated) Protein C (activated)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.69 3.4.21.69] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein_C_(activated) Protein C (activated)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.69 3.4.21.69] </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=3f6u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f6u OCA], [http://pdbe.org/3f6u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3f6u RCSB], [http://www.ebi.ac.uk/pdbsum/3f6u PDBsum]</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=3f6u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f6u OCA], [http://pdbe.org/3f6u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3f6u RCSB], [http://www.ebi.ac.uk/pdbsum/3f6u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3f6u ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 16:		Line 17:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f6/3f6u_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f6/3f6u_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>

OCA at 15:58, 8 February 2016

2016-02-08T15:58:00Z

←Older revision		Revision as of 15:58, 8 February 2016
Line 6:		Line 6:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1aut\|1aut]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1aut\|1aut]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein_C_(activated) Protein C (activated)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.69 3.4.21.69] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein_C_(activated) Protein C (activated)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.69 3.4.21.69] </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=3f6u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f6u OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3f6u RCSB], [http://www.ebi.ac.uk/pdbsum/3f6u PDBsum]</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=3f6u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f6u OCA], [http://pdbe.org/3f6u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3f6u RCSB], [http://www.ebi.ac.uk/pdbsum/3f6u PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 20:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3f6u ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 30:		Line 30:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 3f6u" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 13:12, 18 December 2014

2014-12-18T13:12:21Z

←Older revision		Revision as of 13:12, 18 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3f6u\| PDB=3f6u \| SCENE= }}~~	+	==Crystal structure of human Activated Protein C (APC) complexed with PPACK==
-	===Crystal structure of human Activated Protein C (APC) complexed with PPACK===	+	<StructureSection load='3f6u' size='340' side='right' caption='[[3f6u]], [[Resolution\|resolution]] 2.80Å' scene=''>
-	{~~{ABSTRACT_PUBMED_9003757}~~}	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[3f6u]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3F6U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3F6U FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0G6:D-PHENYLALANYL-N-[(2S,3S)-6-{[AMINO(IMINIO)METHYL]AMINO}-1-CHLORO-2-HYDROXYHEXAN-3-YL]-L-PROLINAMIDE'>0G6</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
-	[[http://www.uniprot.org/uniprot/PROC_HUMAN PROC_HUMAN]] Defects in PROC are the cause of thrombophilia due to protein C deficiency, autosomal dominant (THPH3) [MIM:[http://omim.org/entry/176860 176860]]. A hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. However, many adults with heterozygous disease may be asymptomatic. Individuals with decreased amounts of protein C are classically referred to as having type I protein C deficiency and those with normal amounts of a functionally defective protein as having type II deficiency.<ref>PMID:8560401</ref><ref>PMID:2437584</ref><ref>PMID:2602169</ref><ref>PMID:1868249</ref><ref>PMID:1347706</ref><ref>PMID:1511989</ref><ref>PMID:1301959</ref><ref>PMID:8499568</ref><ref>PMID:8292730</ref><ref>PMID:8398832</ref><ref>PMID:7865674</ref><ref>PMID:7792728</ref><ref>PMID:8829639</ref><ref>PMID:9798967</ref> Defects in PROC are the cause of thrombophilia due to protein C deficiency, autosomal recessive (THPH4) [MIM:[http://omim.org/entry/612304 612304]]. A hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. It results in a thrombotic condition that can manifest as a severe neonatal disorder or as a milder disorder with late-onset thrombophilia. The severe form leads to neonatal death through massive neonatal venous thrombosis. Often associated with ecchymotic skin lesions which can turn necrotic called purpura fulminans, this disorder is very rare.	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1aut\|1aut]]</td></tr>
-		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein_C_(activated) Protein C (activated)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.69 3.4.21.69] </span></td></tr>
-	==Function==	+	<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=3f6u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f6u OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3f6u RCSB], [http://www.ebi.ac.uk/pdbsum/3f6u PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/PROC_HUMAN PROC_HUMAN]] Defects in PROC are the cause of thrombophilia due to protein C deficiency, autosomal dominant (THPH3) [MIM:[http://omim.org/entry/176860 176860]]. A hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. However, many adults with heterozygous disease may be asymptomatic. Individuals with decreased amounts of protein C are classically referred to as having type I protein C deficiency and those with normal amounts of a functionally defective protein as having type II deficiency.<ref>PMID:8560401</ref> <ref>PMID:2437584</ref> <ref>PMID:2602169</ref> <ref>PMID:1868249</ref> <ref>PMID:1347706</ref> <ref>PMID:1511989</ref> <ref>PMID:1301959</ref> <ref>PMID:8499568</ref> <ref>PMID:8292730</ref> <ref>PMID:8398832</ref> <ref>PMID:7865674</ref> <ref>PMID:7792728</ref> <ref>PMID:8829639</ref> <ref>PMID:9798967</ref> Defects in PROC are the cause of thrombophilia due to protein C deficiency, autosomal recessive (THPH4) [MIM:[http://omim.org/entry/612304 612304]]. A hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. It results in a thrombotic condition that can manifest as a severe neonatal disorder or as a milder disorder with late-onset thrombophilia. The severe form leads to neonatal death through massive neonatal venous thrombosis. Often associated with ecchymotic skin lesions which can turn necrotic called purpura fulminans, this disorder is very rare.
		+	== Function ==
	[[http://www.uniprot.org/uniprot/PROC_HUMAN PROC_HUMAN]] Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids.		[[http://www.uniprot.org/uniprot/PROC_HUMAN PROC_HUMAN]] Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids.
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f6/3f6u_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The structure of the Gla-domainless form of the human anticoagulant enzyme activated protein C has been solved at 2.8 A resolution. The light chain is composed of two domains: an epidermal growth factor (EGF)-like domain modified by a large insert containing an additional disulfide, followed by a typical EGF-like domain. The arrangement of the long axis of these domains describes an angle of approximately 80 degrees. Disulfide linked to the light chain is the catalytic domain, which is generally trypsin-like but contains a large insertion loop at the edge of the active site, a third helical segment, a prominent cationic patch analogous to the anion binding exosite I of thrombin and a trypsin-like Ca[II] binding site. The arrangement of loops around the active site partially restricts access to the cleft. The S2 and S4 subsites are much more polar than in factor Xa and thrombin, and the S2 site is unrestricted. While quite open and exposed, the active site contains a prominent groove, the surface of which is very polar with evidence for binding sites on the primed side, in addition to those typical of the trypsin class found on the non-primed side.

-	~~==About this Structure==~~	+	The 2.8 A crystal structure of Gla-domainless activated protein C.,Mather T, Oganessyan V, Hof P, Huber R, Foundling S, Esmon C, Bode W EMBO J. 1996 Dec 16;15(24):6822-31. PMID:9003757<ref>PMID:9003757</ref>
-	~~[[3f6u]] is a~~ 2 ~~chain~~ structure ~~with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens]~~. ~~Full crystallographic information is available from [http~~:/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=3F6U OCA].~~	+

-	~~==Reference==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	<~~ref group="xtra"~~>~~PMID:009003757~~</~~ref~~>~~<ref group~~=~~"xtra">PMID:012029084</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	</div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Bajaj, S P.]]	+	[[Category: Bajaj, S P]]
-	[[Category: Bode, W.]]	+	[[Category: Bode, W]]
-	[[Category: Mather, T.]]	+	[[Category: Mather, T]]
-	[[Category: Padmanabhan, K.]]	+	[[Category: Padmanabhan, K]]
-	[[Category: Schmidt, A E.]]	+	[[Category: Schmidt, A E]]
-	[[Category: Underwood, M C.]]	+	[[Category: Underwood, M C]]
	[[Category: Blood coagulation]]		[[Category: Blood coagulation]]
	[[Category: Hydrolase-hydrolase inhibitor complex]]		[[Category: Hydrolase-hydrolase inhibitor complex]]
	[[Category: Serine protease]]		[[Category: Serine protease]]

OCA at 18:08, 24 March 2013

2013-03-24T18:08:02Z

←Older revision		Revision as of 18:08, 24 March 2013
Line 1:		Line 1:
-	[[Image:3f6u.png\|left\|200px]]
-
	{{STRUCTURE_3f6u\| PDB=3f6u \| SCENE= }}		{{STRUCTURE_3f6u\| PDB=3f6u \| SCENE= }}
-
	===Crystal structure of human Activated Protein C (APC) complexed with PPACK===		===Crystal structure of human Activated Protein C (APC) complexed with PPACK===
		+	{{ABSTRACT_PUBMED_9003757}}

-	~~{{ABSTRACT_PUBMED_9003757}}~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/PROC_HUMAN PROC_HUMAN]] Defects in PROC are the cause of thrombophilia due to protein C deficiency, autosomal dominant (THPH3) [MIM:[http://omim.org/entry/176860 176860]]. A hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. However, many adults with heterozygous disease may be asymptomatic. Individuals with decreased amounts of protein C are classically referred to as having type I protein C deficiency and those with normal amounts of a functionally defective protein as having type II deficiency.<ref>PMID:8560401</ref><ref>PMID:2437584</ref><ref>PMID:2602169</ref><ref>PMID:1868249</ref><ref>PMID:1347706</ref><ref>PMID:1511989</ref><ref>PMID:1301959</ref><ref>PMID:8499568</ref><ref>PMID:8292730</ref><ref>PMID:8398832</ref><ref>PMID:7865674</ref><ref>PMID:7792728</ref><ref>PMID:8829639</ref><ref>PMID:9798967</ref> Defects in PROC are the cause of thrombophilia due to protein C deficiency, autosomal recessive (THPH4) [MIM:[http://omim.org/entry/612304 612304]]. A hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. It results in a thrombotic condition that can manifest as a severe neonatal disorder or as a milder disorder with late-onset thrombophilia. The severe form leads to neonatal death through massive neonatal venous thrombosis. Often associated with ecchymotic skin lesions which can turn necrotic called purpura fulminans, this disorder is very rare.
		+
		+	==Function==
		+	[[http://www.uniprot.org/uniprot/PROC_HUMAN PROC_HUMAN]] Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids.

	==About this Structure==		==About this Structure==
Line 11:		Line 13:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:009003757</ref><ref group="xtra">PMID:012029084</ref><references group="xtra"/>	+	<ref group="xtra">PMID:009003757</ref><ref group="xtra">PMID:012029084</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Bajaj, S P.]]		[[Category: Bajaj, S P.]]

OCA at 12:54, 27 February 2013

2013-02-27T12:54:08Z

←Older revision		Revision as of 12:54, 27 February 2013
Line 1:		Line 1:
	[[Image:3f6u.png\|left\|200px]]		[[Image:3f6u.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_3f6u", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_3f6u\| PDB=3f6u \| SCENE= }}		{{STRUCTURE_3f6u\| PDB=3f6u \| SCENE= }}

	===Crystal structure of human Activated Protein C (APC) complexed with PPACK===		===Crystal structure of human Activated Protein C (APC) complexed with PPACK===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_9003757}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 9003757 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_9003757}}		{{ABSTRACT_PUBMED_9003757}}

OCA at 07:09, 30 October 2011

2011-10-30T07:09:08Z

←Older revision		Revision as of 07:09, 30 October 2011
Line 13:		Line 13:

	<!--		<!--
-	The line below this paragraph, {{~~ABSTRACT_PUBMED_12029084~~}}, adds the Publication Abstract to the page	+	The line below this paragraph, {{ABSTRACT_PUBMED_9003757}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where ~~12029084~~ is the PubMed ID number.	+	(as it appears on PubMed at http://www.pubmed.gov), where 9003757 is the PubMed ID number.
	-->		-->
-	{{~~ABSTRACT_PUBMED_12029084~~}}	+	{{ABSTRACT_PUBMED_9003757}}

	==About this Structure==		==About this Structure==
Line 22:		Line 22:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~012029084~~</ref><ref group="xtra">PMID:~~009003757~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:009003757</ref><ref group="xtra">PMID:012029084</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Bajaj, S P.]]		[[Category: Bajaj, S P.]]

OCA at 04:49, 10 August 2011

2011-08-10T04:49:31Z

←Older revision		Revision as of 04:49, 10 August 2011
Line 19:		Line 19:

	==About this Structure==		==About this Structure==
-	[[3f6u]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3F6U OCA].	+	[[3f6u]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3F6U OCA].

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~12029084~~</ref><ref group="xtra">PMID:~~9003757~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:012029084</ref><ref group="xtra">PMID:009003757</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Bajaj, S P.]]		[[Category: Bajaj, S P.]]
Line 30:		Line 30:
	[[Category: Schmidt, A E.]]		[[Category: Schmidt, A E.]]
	[[Category: Underwood, M C.]]		[[Category: Underwood, M C.]]
-	[[Category: ~~Cleavage on pair of basic residue]]~~	+	[[Category: Blood coagulation]]
-	~~[[Category: Disease mutation]]~~	+	[[Category: Hydrolase-hydrolase inhibitor complex]]
-	~~[[Category: Egf-like domain]]~~	+
-	~~[[Category: Gamma-carboxyglutamic acid]]~~	+
-	~~[[Category: Glycoprotein~~]]	+
-	[[Category: Hydrolase]]	+
-	~~[[Category: Hydroxylation]]~~	+
-	~~[[Category: Plasma calcium binding]]~~	+
-	~~[[Category: Polymorphism]]~~	+
-	~~[[Category: Protease]]~~	+
-	~~[[Category: Re~~-~~refinement]]~~	+
-	~~[[Category: Revised version of the coordinate file pdb 1aut~~]]	+
	[[Category: Serine protease]]		[[Category: Serine protease]]
-	[[Category: Thrombophilia]]
-	[[Category: Zymogen]]