1azx: Difference between revisions

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-[[Image:1azx.png|left|200px]]
-{{STRUCTURE_1azx|  PDB=1azx  |  SCENE=  }}
+==ANTITHROMBIN/PENTASACCHARIDE COMPLEX==
+<StructureSection load='1azx' size='340' side='right'caption='[[1azx]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1azx]] 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=1AZX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AZX 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]] 2.9&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GU1:2,3-DI-O-METHYL-BETA-D-GLUCOPYRANURONIC+ACID'>GU1</scene>, <scene name='pdbligand=GU6:2,3,6-TRI-O-SULFONATO-ALPHA-D-GLUCOPYRANOSE'>GU6</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PRD_900031:heparin+pentasaccharide'>PRD_900031</scene>, <scene name='pdbligand=Z9H:3,4-di-O-methyl-2,6-di-O-sulfo-alpha-D-glucopyranose'>Z9H</scene>, <scene name='pdbligand=Z9K:3-O-methyl-2-O-sulfo-alpha-L-idopyranuronic+acid'>Z9K</scene>, <scene name='pdbligand=Z9L:methyl+2,3,6-tri-O-sulfo-alpha-D-glucopyranoside'>Z9L</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=1azx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1azx OCA], [https://pdbe.org/1azx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1azx RCSB], [https://www.ebi.ac.uk/pdbsum/1azx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1azx 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/az/1azx_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1azx ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Antithrombin, a plasma serpin, is relatively inactive as an inhibitor of the coagulation proteases until it binds to the heparan side chains that line the microvasculature. The binding specifically occurs to a core pentasaccharide present both in the heparans and in their therapeutic derivative heparin. The accompanying conformational change of antithrombin is revealed in a 2.9-A structure of a dimer of latent and active antithrombins, each in complex with the high-affinity pentasaccharide. Inhibitory activation results from a shift in the main sheet of the molecule from a partially six-stranded to a five-stranded form, with extrusion of the reactive center loop to give a more exposed orientation. There is a tilting and elongation of helix D with the formation of a 2-turn helix P between the C and D helices. Concomitant conformational changes at the heparin binding site explain both the initial tight binding of antithrombin to the heparans and the subsequent release of the antithrombin-protease complex into the circulation. The pentasaccharide binds by hydrogen bonding of its sulfates and carboxylates to Arg-129 and Lys-125 in the D-helix, to Arg-46 and Arg-47 in the A-helix, to Lys-114 and Glu-113 in the P-helix, and to Lys-11 and Arg-13 in a cleft formed by the amino terminus. This clear definition of the binding site will provide a structural basis for developing heparin analogues that are more specific toward their intended target antithrombin and therefore less likely to exhibit side effects.
-===ANTITHROMBIN/PENTASACCHARIDE COMPLEX===
+The anticoagulant activation of antithrombin by heparin.,Jin L, Abrahams JP, Skinner R, Petitou M, Pike RN, Carrell RW Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14683-8. PMID:9405673<ref>PMID:9405673</ref>
-{{ABSTRACT_PUBMED_9405673}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 1azx" style="background-color:#fffaf0;"></div>
-[[1azx]] 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=1AZX OCA].
 ==See Also==
-*[[Antithrombin|Antithrombin]]
+*[[Antithrombin 3D structures|Antithrombin 3D structures]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:009405673</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Abrahams, J P.]]
+[[Category: Large Structures]]
-[[Category: Carrell, R W.]]
+[[Category: Abrahams JP]]
-[[Category: Jin, L.]]
+[[Category: Carrell RW]]
-[[Category: Petitou, M.]]
+[[Category: Jin L]]
-[[Category: Pike, R N.]]
+[[Category: Petitou M]]
-[[Category: Skinner, R.]]
+[[Category: Pike RN]]
-[[Category: Anticoagulant activation by heparin]]
+[[Category: Skinner R]]
-[[Category: Antithrombin]]
-[[Category: Serine protease inhibitor]]
-[[Category: Serpin]]