1lk6: Difference between revisions

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-{{Seed}}
-[[Image:1lk6.png|left|200px]]
-<!--
+==Structure of dimeric antithrombin complexed with a P14-P9 reactive loop peptide and an exogenous tripeptide==
-The line below this paragraph, containing "STRUCTURE_1lk6", creates the "Structure Box" on the page.
+<StructureSection load='1lk6' size='340' side='right'caption='[[1lk6]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[1lk6]] is a 4 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=1LK6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LK6 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=FME:N-FORMYLMETHIONINE'>FME</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene></td></tr>
-{{STRUCTURE_1lk6|  PDB=1lk6  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1lk6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lk6 OCA], [https://pdbe.org/1lk6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lk6 RCSB], [https://www.ebi.ac.uk/pdbsum/1lk6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lk6 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/lk/1lk6_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=1lk6 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Polymerization of serpins commonly results from mutations in the shutter region underlying the bifurcation of strands 3 and 5 of the A-sheet, with entry beyond this point being barred by a H-bond network centered on His-334. Exposure of this histidine in antithrombin, which has a partially opened sheet, allows polymerization and peptide insertion to occur at pH 6 or less when His-334 will be predictably protonated with disruption of the H-bond network. Similarly, thermal stability of antithrombin is pH-dependent with a single unfolding transition at pH 6, but there is no such transition when His-334 is buried by a fully closed A-sheet in heparin-complexed antithrombin or in alpha(1)-antitrypsin. Replacement of His-334 in alpha(1)-antitrypsin by a serine or alanine at pH 7.4 results in the same polymerization and loop-peptide acceptance observed with antithrombin at low pH. The critical role of His-334 and the re-formation of its H-bond network by the conserved P8 threonine, on the full insertion of strand 4, are relevant for the design of therapeutic blocking agents. This is highlighted here by the crystallographic demonstration that glycerol, which at high concentrations blocks polymerization, can replace the P8 threonine and re-form the disrupted H-bond network with His-334.
-===Structure of dimeric antithrombin complexed with a P14-P9 reactive loop peptide and an exogenous tripeptide===
+Serpin polymerization is prevented by a hydrogen bond network that is centered on his-334 and stabilized by glycerol.,Zhou A, Stein PE, Huntington JA, Carrell RW J Biol Chem. 2003 Apr 25;278(17):15116-22. Epub 2003 Feb 10. PMID:12578831<ref>PMID:12578831</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 1lk6" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_12578831}}, adds the Publication Abstract to the page
+*[[Antithrombin 3D structures|Antithrombin 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 12578831 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_12578831}}
+__TOC__
+</StructureSection>
-==About this Structure==
-LK6 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=1LK6 OCA].
-==Reference==
-Serpin polymerization is prevented by a hydrogen bond network that is centered on his-334 and stabilized by glycerol., Zhou A, Stein PE, Huntington JA, Carrell RW, J Biol Chem. 2003 Apr 25;278(17):15116-22. Epub 2003 Feb 10. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12578831 12578831]
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Carrell, R W.]]
+[[Category: Carrell RW]]
-[[Category: Huntington, J A.]]
+[[Category: Huntington JA]]
-[[Category: Lomas, D A.]]
+[[Category: Lomas DA]]
-[[Category: Stein, P E.]]
+[[Category: Stein PE]]
-[[Category: Zhou, A.]]
+[[Category: Zhou A]]
-[[Category: Beta-barell]]
-[[Category: Loop-sheet polymer]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul  2 21:16:58 2008''