2beh: Difference between revisions

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-[[Image:2beh.png|left|200px]]
-{{STRUCTURE_2beh|  PDB=2beh  |  SCENE=  }}
+==Crystal structure of antithrombin variant S137A/V317C/T401C with plasma latent antithrombin==
+<StructureSection load='2beh' size='340' side='right'caption='[[2beh]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2beh]] 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=2BEH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BEH FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=2beh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2beh OCA], [https://pdbe.org/2beh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2beh RCSB], [https://www.ebi.ac.uk/pdbsum/2beh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2beh ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[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>
+== Function ==
+[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>
+== 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/be/2beh_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/main_output.php?pdb_ID=2beh ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The poor inhibitory activity of circulating antithrombin (AT) is critical to the formation of blood clots at sites of vascular damage. AT becomes an efficient inhibitor of the coagulation proteases only after binding to a specific heparin pentasaccharide, which alters the conformation of the reactive center loop (RCL). The molecular basis of this activation event lies at the heart of the regulation of hemostasis and accounts for the anticoagulant properties of the low molecular weight heparins. Although several structures of AT have been solved, the conformation of the RCL in native AT remains unknown because of the obligate crystal contact between the RCL of native AT and its latent counterpart. Here we report the crystallographic structure of a variant of AT in its monomeric native state. The RCL shifted approximately 20 A, and a salt bridge was observed between the P1 residue (Arg-393) and Glu-237. This contact explains the effect of mutations at the P1 position on the affinity of AT for heparin and also the properties of AT-Truro (E237K). The relevance of the observed conformation was verified through mutagenesis studies and by solving structures of the same variant in different crystal forms. We conclude that the poor inhibitory activity of the circulating form of AT is partially conferred by intramolecular contacts that restrain the RCL, orient the P1 residue away from attacking proteases, and additionally block the exosite utilized in protease recognition.
-===Crystal structure of antithrombin variant S137A/V317C/T401C with plasma latent antithrombin===
+Crystal structure of monomeric native antithrombin reveals a novel reactive center loop conformation.,Johnson DJ, Langdown J, Li W, Luis SA, Baglin TP, Huntington JA J Biol Chem. 2006 Nov 17;281(46):35478-86. Epub 2006 Sep 13. PMID:16973611<ref>PMID:16973611</ref>
-{{ABSTRACT_PUBMED_16973611}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 2beh" style="background-color:#fffaf0;"></div>
-[[2beh]] is a 2 chain structure of [[Antithrombin]] 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=2BEH OCA].
 ==See Also==
-*[[Antithrombin|Antithrombin]]
+*[[Antithrombin 3D structures|Antithrombin 3D structures]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:016973611</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Huntington, J A.]]
+[[Category: Large Structures]]
-[[Category: Johnson, D J.]]
+[[Category: Huntington JA]]
-[[Category: Luis, S A.]]
+[[Category: Johnson DJ]]
-[[Category: Antithrombin dimer]]
+[[Category: Luis SA]]
-[[Category: Blood clotting]]