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1jmj

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(New page: 200px<br /> <applet load="1jmj" size="450" color="white" frame="true" align="right" spinBox="true" caption="1jmj, resolution 2.35&Aring;" /> '''Crystal Structure o...)
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[[Image:1jmj.gif|left|200px]]<br />
 
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<applet load="1jmj" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1jmj, resolution 2.35&Aring;" />
 
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'''Crystal Structure of Native Heparin Cofactor II'''<br />
 
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==Overview==
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==Crystal Structure of Native Heparin Cofactor II==
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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.
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<StructureSection load='1jmj' size='340' side='right'caption='[[1jmj]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
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== Structural highlights ==
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==Disease==
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<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>
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Known diseases associated with this structure: Thrombophilia due to heparin cofactor II deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142360 142360]]
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.35&#8491;</td></tr>
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<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>
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==About this Structure==
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<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>
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1JMJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG and CA as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1JMJ OCA].
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</table>
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== Disease ==
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==Reference==
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[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>
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12169660 12169660]
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== Function ==
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jm/1jmj_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1jmj ConSurf].
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<div style="clear:both"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Baglin, T.P.]]
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[[Category: Baglin TP]]
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[[Category: Carrell, R.W.]]
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[[Category: Carrell RW]]
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[[Category: Church, F.C.]]
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[[Category: Church FC]]
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[[Category: Huntington, J.A.]]
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[[Category: Huntington JA]]
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[[Category: CA]]
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[[Category: NAG]]
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[[Category: heparin]]
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[[Category: serpin]]
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[[Category: thrombin inhibitor]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:42:29 2007''
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Current revision

Crystal Structure of Native Heparin Cofactor II

PDB ID 1jmj

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