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1ant

From Proteopedia

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(New page: 200px<br /> <applet load="1ant" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ant, resolution 3.0&Aring;" /> '''BIOLOGICAL IMPLICATI...)
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[[Image:1ant.gif|left|200px]]<br />
 
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<applet load="1ant" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1ant, resolution 3.0&Aring;" />
 
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'''BIOLOGICAL IMPLICATIONS OF A 3 ANGSTROMS STRUCTURE OF DIMERIC ANTITHROMBIN'''<br />
 
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==Overview==
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==BIOLOGICAL IMPLICATIONS OF A 3 ANGSTROMS STRUCTURE OF DIMERIC ANTITHROMBIN==
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BACKGROUND: Antithrombin, a member of the serpin family of inhibitors, controls coagulation in human plasma by forming complexes with thrombin, and other coagulation proteases in a process greatly accelerated by, heparin. The structures of several serpins have been determined but not in, their active conformations. We have determined the structure of intact, antithrombin in order to study its mechanism of activation, particularly, with respect to heparin, and the dysfunctions of this mechanism that, predispose individuals to thrombotic disease. RESULTS: The crystal, structure of a dimer of one active and one inactive molecule of, antithrombin has been determined at 3 A. The first molecule has its, reactive-centre loop in a predicted active conformation compatible with, initial entry of two residues into the main beta-sheet of the molecule., The inactive molecule has a totally incorporated loop as in latent, plasminogen activator inhibitor-1. The two molecules are linked by the, reactive loop of the active molecule which has replaced a strand from, another beta-sheet in the latent molecule. CONCLUSION: The structure, together with identified mutations affecting its heparin affinity, allows, the placement of the heparin-binding site on the molecule. The, conformation of the two forms of antithrombin demonstrates the, extraordinary mobility of the reactive loop in the serpins and provides, insights into the folding of the loop required for inhibitory activity, together with the potential modification of this by heparin. The mechanism, of dimerization is relevant to the polymerization that is observed in, diseases associated with variant serpins.
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<StructureSection load='1ant' size='340' side='right'caption='[[1ant]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1ant]] 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=1ANT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ANT 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&#8491;</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=1ant FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ant OCA], [https://pdbe.org/1ant PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ant RCSB], [https://www.ebi.ac.uk/pdbsum/1ant PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ant 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/an/1ant_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=1ant ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1ANT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1ANT OCA].
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*[[Antithrombin 3D structures|Antithrombin 3D structures]]
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== References ==
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==Reference==
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<references/>
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Biological implications of a 3 A structure of dimeric antithrombin., Carrell RW, Stein PE, Fermi G, Wardell MR, Structure. 1994 Apr 15;2(4):257-70. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=8087553 8087553]
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__TOC__
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</StructureSection>
[[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: Carrell, R.W.]]
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[[Category: Carrell RW]]
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[[Category: Fermi, G.]]
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[[Category: Fermi G]]
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[[Category: Stein, P.E.]]
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[[Category: Stein PE]]
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[[Category: Wardell, M.R.]]
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[[Category: Wardell MR]]
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[[Category: serine protease inhibitor]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 16:00:16 2007''
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Current revision

BIOLOGICAL IMPLICATIONS OF A 3 ANGSTROMS STRUCTURE OF DIMERIC ANTITHROMBIN

PDB ID 1ant

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