1jmj

From Proteopedia

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Revision as of 06:42, 11 August 2021

Crystal Structure of Native Heparin Cofactor II

Structural highlights

1jmj is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	1jmo
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[HEP2_HUMAN] Defects in SERPIND1 are the cause of thrombophilia due to heparin cofactor 2 deficiency (THPH10) [MIM:612356]. A hemostatic disorder characterized by a tendency to recurrent thrombosis.^[1] ^[2] ^[3] ^[4]

Function

[HEP2_HUMAN] Thrombin inhibitor activated by the glycosaminoglycans, heparin or dermatan sulfate. In the presence of the latter, HC-II becomes the predominant thrombin inhibitor in place of antithrombin III (AT-III). Also inhibits chymotrypsin, but in a glycosaminoglycan-independent manner.^[5] Peptides at the N-terminal of HC-II have chemotactic activity for both monocytes and neutrophils.^[6]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The serine proteases sequentially activated to form a fibrin clot are inhibited primarily by members of the serpin family, which use a unique beta-sheet expansion mechanism to trap and destroy their targets. Since the discovery that serpins were a family of serine protease inhibitors there has been controversy as to the role of conformational change in their mechanism. It now is clear that protease inhibition depends entirely on rapid serpin beta-sheet expansion after proteolytic attack. The regulatory advantage afforded by the conformational mobility of serpins is demonstrated here by the structures of native and S195A thrombin-complexed heparin cofactor II (HCII). HCII inhibits thrombin, the final protease of the coagulation cascade, in a glycosaminoglycan-dependent manner that involves the release of a sequestered hirudin-like N-terminal tail for interaction with thrombin. The native structure of HCII resembles that of native antithrombin and suggests an alternative mechanism of allosteric activation, whereas the structure of the S195A thrombin-HCII complex defines the molecular basis of allostery. Together, these structures reveal a multistep allosteric mechanism that relies on sequential contraction and expansion of the central beta-sheet of HCII.

Crystal structures of native and thrombin-complexed heparin cofactor II reveal a multistep allosteric mechanism.,Baglin TP, Carrell RW, Church FC, Esmon CT, Huntington JA Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11079-84. Epub 2002 Aug 8. PMID:12169660^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Blinder MA, Andersson TR, Abildgaard U, Tollefsen DM. Heparin cofactor IIOslo. Mutation of Arg-189 to His decreases the affinity for dermatan sulfate. J Biol Chem. 1989 Mar 25;264(9):5128-33. PMID:2647747
↑ Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES. Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. PMID:10391209 doi:10.1038/10290
↑ Kanagawa Y, Shigekiyo T, Aihara K, Akaike M, Azuma H, Matsumoto T. Molecular mechanism of type I congenital heparin cofactor (HC) II deficiency caused by a missense mutation at reactive P2 site: HC II Tokushima. Thromb Haemost. 2001 Jan;85(1):101-7. PMID:11204559
↑ Corral J, Aznar J, Gonzalez-Conejero R, Villa P, Minano A, Vaya A, Carrell RW, Huntington JA, Vicente V. Homozygous deficiency of heparin cofactor II: relevance of P17 glutamate residue in serpins, relationship with conformational diseases, and role in thrombosis. Circulation. 2004 Sep 7;110(10):1303-7. Epub 2004 Aug 30. PMID:15337701 doi:10.1161/01.CIR.0000140763.51679.D9
↑ Van Deerlin VM, Tollefsen DM. The N-terminal acidic domain of heparin cofactor II mediates the inhibition of alpha-thrombin in the presence of glycosaminoglycans. J Biol Chem. 1991 Oct 25;266(30):20223-31. PMID:1939083
↑ Van Deerlin VM, Tollefsen DM. The N-terminal acidic domain of heparin cofactor II mediates the inhibition of alpha-thrombin in the presence of glycosaminoglycans. J Biol Chem. 1991 Oct 25;266(30):20223-31. PMID:1939083
↑ Baglin TP, Carrell RW, Church FC, Esmon CT, Huntington JA. Crystal structures of native and thrombin-complexed heparin cofactor II reveal a multistep allosteric mechanism. Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11079-84. Epub 2002 Aug 8. PMID:12169660 doi:10.1073/pnas.162232399

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1jmj"

@@ Line 3: / Line 3: @@
 <StructureSection load='1jmj' size='340' side='right'caption='[[1jmj]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1jmj]] 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=1JMJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1JMJ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1jmj]] 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=1JMJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JMJ FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1jmo|1jmo]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1jmo|1jmo]]</div></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=1jmj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jmj OCA], [http://pdbe.org/1jmj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1jmj RCSB], [http://www.ebi.ac.uk/pdbsum/1jmj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1jmj 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=1jmj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jmj OCA], [https://pdbe.org/1jmj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1jmj RCSB], [https://www.ebi.ac.uk/pdbsum/1jmj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1jmj ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/HEP2_HUMAN HEP2_HUMAN]] Defects in SERPIND1 are the cause of thrombophilia due to heparin cofactor 2 deficiency (THPH10) [MIM:[http://omim.org/entry/612356 612356]]. A hemostatic disorder characterized by a tendency to recurrent thrombosis.<ref>PMID:2647747</ref> <ref>PMID:10391209</ref> <ref>PMID:11204559</ref> <ref>PMID:15337701</ref>
+[[https://www.uniprot.org/uniprot/HEP2_HUMAN HEP2_HUMAN]] Defects in SERPIND1 are the cause of thrombophilia due to heparin cofactor 2 deficiency (THPH10) [MIM:[https://omim.org/entry/612356 612356]]. A hemostatic disorder characterized by a tendency to recurrent thrombosis.<ref>PMID:2647747</ref> <ref>PMID:10391209</ref> <ref>PMID:11204559</ref> <ref>PMID:15337701</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/HEP2_HUMAN HEP2_HUMAN]] Thrombin inhibitor activated by the glycosaminoglycans, heparin or dermatan sulfate. In the presence of the latter, HC-II becomes the predominant thrombin inhibitor in place of antithrombin III (AT-III). Also inhibits chymotrypsin, but in a glycosaminoglycan-independent manner.<ref>PMID:1939083</ref>   Peptides at the N-terminal of HC-II have chemotactic activity for both monocytes and neutrophils.<ref>PMID:1939083</ref>
+[[https://www.uniprot.org/uniprot/HEP2_HUMAN HEP2_HUMAN]] Thrombin inhibitor activated by the glycosaminoglycans, heparin or dermatan sulfate. In the presence of the latter, HC-II becomes the predominant thrombin inhibitor in place of antithrombin III (AT-III). Also inhibits chymotrypsin, but in a glycosaminoglycan-independent manner.<ref>PMID:1939083</ref>   Peptides at the N-terminal of HC-II have chemotactic activity for both monocytes and neutrophils.<ref>PMID:1939083</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

1jmj

From Proteopedia

Revision as of 06:42, 11 August 2021

Crystal Structure of Native Heparin Cofactor II

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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