View source for 2ant


==THE 2.6 A STRUCTURE OF ANTITHROMBIN INDICATES A CONFORMATIONAL CHANGE AT THE HEPARIN BINDING SITE==
<StructureSection load='2ant' size='340' side='right'caption='[[2ant]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2ant]] 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=2ANT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ANT 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]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAA:N-ACETYL-D-ALLOSAMINE'>NAA</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=2ant FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ant OCA], [https://pdbe.org/2ant PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ant RCSB], [https://www.ebi.ac.uk/pdbsum/2ant PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ant ProSAT]</span></td></tr>
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== 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/an/2ant_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=2ant ConSurf].
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== Publication Abstract from PubMed ==
The crystal structure of a dimeric form of intact antithrombin has been solved to 2.6 A, representing the highest-resolution structure of an active, inhibitory serpin to date. The crystals were grown under microgravity conditions on Space Shuttle mission STS-67. The overall confidence in the structure, determined earlier from lower resolution data, is increased and new insights into the structure-function relationship are gained. Clear and continuous electron density is present for the reactive centre loop region P12 to P14 inserting into the top of the A-beta-sheet. Areas of the extended amino terminus, unique to antithrombin and important in the binding of the glycosaminoglycan heparin, can now be traced further than in the earlier structures. As in the earlier studies, the crystals contain one active and one latent molecule per asymmetric unit. Better definition of the electron density surrounding the D-helix and of the residues implicated in the binding of the heparin pentasaccharide (Arg47, Lys114, Lys125, Arg129) provides an insight into the change of affinity of binding that accompanies the change in conformation. In particular, the observed hydrogen bonding of these residues to the body of the molecule in the latent form explains the mechanism for the release of newly formed antithrombin-protease complexes into the circulation for catabolic removal.

The 2.6 A structure of antithrombin indicates a conformational change at the heparin binding site.,Skinner R, Abrahams JP, Whisstock JC, Lesk AM, Carrell RW, Wardell MR J Mol Biol. 1997 Feb 28;266(3):601-9. PMID:9067613<ref>PMID:9067613</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2ant" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antithrombin 3D structures|Antithrombin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Abrahams J-P]]
[[Category: Carrell RW]]
[[Category: Lesk AM]]
[[Category: Skinner R]]
[[Category: Wardell MR]]
[[Category: Whisstock JC]]