1sr5

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[[Image:1sr5.png|left|200px]]
 
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{{STRUCTURE_1sr5| PDB=1sr5 | SCENE= }}
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==ANTITHROMBIN-ANHYDROTHROMBIN-HEPARIN TERNARY COMPLEX STRUCTURE==
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<StructureSection load='1sr5' size='340' side='right'caption='[[1sr5]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1sr5]] is a 3 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=1SR5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SR5 FirstGlance]. <br>
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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]] 3.1&#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=GU4:2,3,4,6-TETRA-O-SULFONATO-ALPHA-D-GLUCOPYRANOSE'>GU4</scene>, <scene name='pdbligand=GU6:2,3,6-TRI-O-SULFONATO-ALPHA-D-GLUCOPYRANOSE'>GU6</scene>, <scene name='pdbligand=GU8:2,3,6-TRI-O-METHYL-BETA-D-GLUCOPYRANOSE'>GU8</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=U9D:4-deoxy-2,3,6-tri-O-methyl-alpha-D-xylo-hexopyranose'>U9D</scene>, <scene name='pdbligand=U9G:[(2~{R},3~{R},4~{S},5~{R},6~{S})-4,5-dimethoxy-3,6-bis(oxidanyl)oxan-2-yl]methyl+hydrogen+sulfate'>U9G</scene>, <scene name='pdbligand=U9J:(2~{R},3~{R},4~{S},5~{S},6~{R})-6-[bis(oxidanyl)methyl]-3,4-dimethoxy-oxane-2,5-diol'>U9J</scene>, <scene name='pdbligand=U9M:(2~{R},3~{R},4~{S},5~{S},6~{S})-6-[bis(oxidanyl)methyl]-3,4-dimethoxy-oxane-2,5-diol'>U9M</scene>, <scene name='pdbligand=YYB:[(3S,4S,5R,6R)-4-methoxy-5-oxidanyl-6-(sulfooxymethyl)oxan-3-yl]+hydrogen+sulfate'>YYB</scene></td></tr>
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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=1sr5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sr5 OCA], [https://pdbe.org/1sr5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1sr5 RCSB], [https://www.ebi.ac.uk/pdbsum/1sr5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1sr5 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/ANT3_HUMAN ANT3_HUMAN] Defects in SERPINC1 are the cause of antithrombin III deficiency (AT3D) [MIM:[https://omim.org/entry/613118 613118]. AT3D is an important risk factor for hereditary thrombophilia, a hemostatic disorder characterized by a tendency to recurrent thrombosis. AT3D is classified into 4 types. Type I: characterized by a 50% decrease in antigenic and functional levels. Type II: has defects affecting the thrombin-binding domain. Type III: alteration of the heparin-binding domain. Plasma AT-III antigen levels are normal in type II and III. Type IV: consists of miscellaneous group of unclassifiable mutations.<ref>PMID:7734359</ref> [:]<ref>PMID:3191114</ref> <ref>PMID:9031473</ref> <ref>PMID:6582486</ref> <ref>PMID:3080419</ref> <ref>PMID:3805013</ref> <ref>PMID:3179438</ref> <ref>PMID:3162733</ref> <ref>PMID:2781509</ref> <ref>PMID:2365065</ref> <ref>PMID:2229057</ref> <ref>PMID:2013320</ref> <ref>PMID:1906811</ref> <ref>PMID:1555650</ref> <ref>PMID:1547341</ref> <ref>PMID:8443391</ref> <ref>PMID:8486379</ref> <ref>PMID:7981186</ref> <ref>PMID:7959685</ref> <ref>PMID:8274732</ref> <ref>PMID:7994035</ref> <ref>PMID:7989582</ref> [:]<ref>PMID:7878627</ref> <ref>PMID:7832187</ref> <ref>PMID:9157604</ref> <ref>PMID:9845533</ref> <ref>PMID:9759613</ref> <ref>PMID:10997988</ref> <ref>PMID:11794707</ref> <ref>PMID:11713457</ref> <ref>PMID:12353073</ref> <ref>PMID:12595305</ref> <ref>PMID:12894857</ref> <ref>PMID:15164384</ref> <ref>PMID:16908819</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/ANT3_HUMAN ANT3_HUMAN] Most important serine protease inhibitor in plasma that regulates the blood coagulation cascade. AT-III inhibits thrombin, matriptase-3/TMPRSS7, as well as factors IXa, Xa and XIa. Its inhibitory activity is greatly enhanced in the presence of heparin.<ref>PMID:15853774</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/sr/1sr5_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1sr5 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Antithrombin, the principal physiological inhibitor of the blood coagulation proteinase thrombin, requires heparin as a cofactor. We report the crystal structure of the rate-determining encounter complex formed between antithrombin, anhydrothrombin and an optimal synthetic 16-mer oligosaccharide. The antithrombin reactive center loop projects from the serpin body and adopts a canonical conformation that makes extensive backbone and side chain contacts from P5 to P6' with thrombin's restrictive specificity pockets, including residues in the 60-loop. These contacts rationalize many earlier mutagenesis studies on thrombin specificity. The 16-mer oligosaccharide is just long enough to form the predicted bridge between the high-affinity pentasaccharide-binding site on antithrombin and the highly basic exosite 2 on thrombin, validating the design strategy for this synthetic heparin. The protein-protein and protein-oligosaccharide interactions together explain the basis for heparin activation of antithrombin as a thrombin inhibitor.
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===ANTITHROMBIN-ANHYDROTHROMBIN-HEPARIN TERNARY COMPLEX STRUCTURE===
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The ternary complex of antithrombin-anhydrothrombin-heparin reveals the basis of inhibitor specificity.,Dementiev A, Petitou M, Herbert JM, Gettins PG Nat Struct Mol Biol. 2004 Sep;11(9):863-7. Epub 2004 Aug 15. PMID:15311268<ref>PMID:15311268</ref>
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{{ABSTRACT_PUBMED_15311268}}
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==About this Structure==
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<div class="pdbe-citations 1sr5" style="background-color:#fffaf0;"></div>
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[[1sr5]] 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=1SR5 OCA].
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==See Also==
==See Also==
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*[[Antithrombin|Antithrombin]]
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*[[Antithrombin 3D structures|Antithrombin 3D structures]]
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*[[Thrombin 3D Structures|Thrombin 3D Structures]]
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==Reference==
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== References ==
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<ref group="xtra">PMID:015311268</ref><ref group="xtra">PMID:016673263</ref><references group="xtra"/>
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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: Thrombin]]
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[[Category: Large Structures]]
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[[Category: Dementiev, A.]]
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[[Category: Dementiev A]]
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[[Category: Gettins, P G.]]
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[[Category: Gettins PG]]
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[[Category: Petitou, M.]]
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[[Category: Petitou M]]
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[[Category: Antithrombin activation by hep anhydrothrombin]]
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[[Category: Hydrolase-hydrolase inhibitor complex]]
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[[Category: Protein-protein interaction]]
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[[Category: Serine proteinase inhibitor]]
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Current revision

ANTITHROMBIN-ANHYDROTHROMBIN-HEPARIN TERNARY COMPLEX STRUCTURE

PDB ID 1sr5

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