3hk3: Difference between revisions

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-{{Seed}}
-[[Image:3hk3.png|left|200px]]
-<!--
+==Crystal structure of murine thrombin mutant W215A/E217A (one molecule in the asymmetric unit)==
-The line below this paragraph, containing "STRUCTURE_3hk3", creates the "Structure Box" on the page.
+<StructureSection load='3hk3' size='340' side='right'caption='[[3hk3]], [[Resolution|resolution]] 1.94&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'>[[3hk3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HK3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HK3 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]] 1.94&#8491;</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=3hk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hk3 OCA], [https://pdbe.org/3hk3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hk3 RCSB], [https://www.ebi.ac.uk/pdbsum/3hk3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hk3 ProSAT]</span></td></tr>
-{{STRUCTURE_3hk3|  PDB=3hk3  |  SCENE=  }}
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/THRB_MOUSE THRB_MOUSE] Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing (By similarity).
+== 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/hk/3hk3_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=3hk3 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The thrombin mutant W215A/E217A (WE) is a potent anticoagulant both in vitro and in vivo. Previous x-ray structural studies have shown that WE assumes a partially collapsed conformation that is similar to the inactive E* form, which explains its drastically reduced activity toward substrate. Whether this collapsed conformation is genuine, rather than the result of crystal packing or the mutation introduced in the critical 215-217 beta-strand, and whether binding of thrombomodulin to exosite I can allosterically shift the E* form to the active E form to restore activity toward protein C are issues of considerable mechanistic importance to improve the design of an anticoagulant thrombin mutant for therapeutic applications. Here we present four crystal structures of WE in the human and murine forms that confirm the collapsed conformation reported previously under different experimental conditions and crystal packing. We also present structures of human and murine WE bound to exosite I with a fragment of the platelet receptor PAR1, which is unable to shift WE to the E form. These structural findings, along with kinetic and calorimetry data, indicate that WE is strongly stabilized in the E* form and explain why binding of ligands to exosite I has only a modest effect on the E*-E equilibrium for this mutant. The E* --&gt; E transition requires the combined binding of thrombomodulin and protein C and restores activity of the mutant WE in the anticoagulant pathway.
-===Crystal structure of murine thrombin mutant W215A/E217A (one molecule in the asymmetric unit)===
+Mechanism of the anticoagulant activity of thrombin mutant W215A/E217A.,Gandhi PS, Page MJ, Chen Z, Bush-Pelc L, Di Cera E J Biol Chem. 2009 Sep 4;284(36):24098-105. Epub 2009 Jul 8. PMID:19586901<ref>PMID:19586901</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3hk3" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_19586901}}, adds the Publication Abstract to the page
+*[[Thrombin 3D Structures|Thrombin 3D Structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 19586901 is the PubMed ID number.
+*[[Thrombin heavy chain|Thrombin heavy chain]]
--->
+*[[Thrombin light chain|Thrombin light chain]]
-{{ABSTRACT_PUBMED_19586901}}
+== References ==
+<references/>
-==About this Structure==
+__TOC__
-HK3 is a 2 chains structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HK3 OCA].
+</StructureSection>
+[[Category: Large Structures]]
-==Reference==
-<ref group="xtra">PMID:19586901</ref><ref group="xtra">PMID:15252033</ref><references group="xtra"/>
 [[Category: Mus musculus]]
-[[Category: Thrombin]]
+[[Category: Bush-Pelc L]]
-[[Category: Bush-Pelc, L.]]
+[[Category: Chen Z]]
-[[Category: Cera, E Di.]]
+[[Category: Di Cera E]]
-[[Category: Chen, Z.]]
+[[Category: Gandhi PS]]
-[[Category: Gandhi, P S.]]
+[[Category: Page MJ]]
-[[Category: Page, M J.]]
-[[Category: Acute phase]]
-[[Category: Blood coagulation]]
-[[Category: Calcium]]
-[[Category: Cleavage on pair of basic residue]]
-[[Category: Disulfide bond]]
-[[Category: Gamma-carboxyglutamic acid]]
-[[Category: Glycoprotein]]
-[[Category: Hydrolase]]
-[[Category: Kringle]]
-[[Category: Protease]]
-[[Category: Serine protease]]
-[[Category: Zymogen]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Sep 16 08:35:19 2009''