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1azx

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[[Image:1azx.gif|left|200px]]
 
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{{Structure
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==ANTITHROMBIN/PENTASACCHARIDE COMPLEX==
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|PDB= 1azx |SIZE=350|CAPTION= <scene name='initialview01'>1azx</scene>, resolution 2.9&Aring;
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<StructureSection load='1azx' size='340' side='right'caption='[[1azx]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene> and <scene name='pdbligand=NTP:HEPARIN PENTASACCHARIDE'>NTP</scene>
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<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>
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|ACTIVITY=
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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]] 2.9&#8491;</td></tr>
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|GENE=
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<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>
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}}
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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=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>
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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/az/1azx_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=1azx ConSurf].
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<div style="clear:both"></div>
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'''ANTITHROMBIN/PENTASACCHARIDE COMPLEX'''
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==See Also==
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*[[Antithrombin 3D structures|Antithrombin 3D structures]]
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== References ==
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==Overview==
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<references/>
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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.
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__TOC__
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</StructureSection>
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==About this Structure==
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1AZX is a [[Single protein]] structure of 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].
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==Reference==
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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:[http://www.ncbi.nlm.nih.gov/pubmed/9405673 9405673]
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[[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: Abrahams, J P.]]
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[[Category: Abrahams JP]]
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[[Category: Carrell, R W.]]
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[[Category: Carrell RW]]
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[[Category: Jin, L.]]
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[[Category: Jin L]]
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[[Category: Petitou, M.]]
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[[Category: Petitou M]]
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[[Category: Pike, R N.]]
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[[Category: Pike RN]]
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[[Category: Skinner, R.]]
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[[Category: Skinner R]]
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[[Category: NAG]]
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[[Category: NTP]]
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[[Category: anticoagulant activation by heparin]]
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[[Category: antithrombin]]
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[[Category: serine protease inhibitor]]
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[[Category: serpin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:04:27 2008''
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Current revision

ANTITHROMBIN/PENTASACCHARIDE COMPLEX

PDB ID 1azx

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