7sr9

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Current revision (16:54, 18 October 2023) (edit) (undo)
 
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==Human alpha-thrombin with 180- and 220- loops replaced with homologous loops from protein C==
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<StructureSection load='7sr9' size='340' side='right'caption='[[7sr9]]' scene=''>
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<StructureSection load='7sr9' size='340' side='right'caption='[[7sr9]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
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<table><tr><td colspan='2'>[[7sr9]] 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=7SR9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SR9 FirstGlance]. <br>
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</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=7sr9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sr9 OCA], [https://pdbe.org/7sr9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sr9 RCSB], [https://www.ebi.ac.uk/pdbsum/7sr9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sr9 ProSAT]</span></td></tr>
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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]] 2.1&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=7sr9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sr9 OCA], [https://pdbe.org/7sr9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sr9 RCSB], [https://www.ebi.ac.uk/pdbsum/7sr9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sr9 ProSAT]</span></td></tr>
</table>
</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN] Defects in F2 are the cause of factor II deficiency (FA2D) [MIM:[https://omim.org/entry/613679 613679]. It is a very rare blood coagulation disorder characterized by mucocutaneous bleeding symptoms. The severity of the bleeding manifestations correlates with blood factor II levels.<ref>PMID:14962227</ref> <ref>PMID:6405779</ref> <ref>PMID:3771562</ref> <ref>PMID:3567158</ref> <ref>PMID:3801671</ref> <ref>PMID:3242619</ref> <ref>PMID:2719946</ref> <ref>PMID:1354985</ref> <ref>PMID:1421398</ref> <ref>PMID:1349838</ref> <ref>PMID:7865694</ref> <ref>PMID:7792730</ref> Genetic variations in F2 may be a cause of susceptibility to ischemic stroke (ISCHSTR) [MIM:[https://omim.org/entry/601367 601367]; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.<ref>PMID:15534175</ref> Defects in F2 are the cause of thrombophilia due to thrombin defect (THPH1) [MIM:[https://omim.org/entry/188050 188050]. It is a multifactorial disorder of hemostasis characterized by abnormal platelet aggregation in response to various agents and recurrent thrombi formation. Note=A common genetic variation in the 3-prime untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increased risk of venous thrombosis. Defects in F2 are associated with susceptibility to pregnancy loss, recurrent, type 2 (RPRGL2) [MIM:[https://omim.org/entry/614390 614390]. A common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined as 3 or more consecutive spontaneous abortions.<ref>PMID:11506076</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN] 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.<ref>PMID:2856554</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The catalytic activity of thrombin and other enzymes of the blood coagulation and complement cascades is enhanced significantly by binding of Na(+) to a site &gt;15 A away from the catalytic residue S195, buried within the 180 and 220 loops that also contribute to the primary specificity of the enzyme. Rapid kinetics support a binding mechanism of conformational selection where the Na(+)-binding site is in equilibrium between open (N) and closed (N( *)) forms and the cation binds selectively to the N form. Allosteric transduction of this binding step produces enhanced catalytic activity. Molecular details on how Na(+) gains access to this site and communicates allosterically with the active site remain poorly defined. In this study, we show that the rate of the N( *)--&gt;N transition is strongly correlated with the analogous E( *)--&gt;E transition that governs the interaction of synthetic and physiologic substrates with the active site. This correlation supports the active site as the likely point of entry for Na(+) to its binding site. Mutagenesis and structural data rule out an alternative path through the pore defined by the 180 and 220 loops. We suggest that the active site communicates allosterically with the Na(+) site through a network of H-bonded water molecules that embeds the primary specificity pocket. Perturbation of the mobility of S195 and its H-bonding capabilities alters interaction with this network and influences the kinetics of Na(+) binding and allosteric transduction. These findings have general mechanistic relevance for Na(+)-activated proteases and allosteric enzymes.
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The active site region plays a critical role in Na(+) binding to thrombin.,Pelc LA, Koester SK, Kukla CR, Chen Z, Di Cera E J Biol Chem. 2022 Jan;298(1):101458. doi: 10.1016/j.jbc.2021.101458. Epub 2021 , Nov 30. PMID:34861239<ref>PMID:34861239</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 7sr9" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Thrombin 3D Structures|Thrombin 3D Structures]]
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Z-disk]]
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[[Category: Chen Z]]
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[[Category: Di Cera E]]
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[[Category: Ruben EA]]

Current revision

Human alpha-thrombin with 180- and 220- loops replaced with homologous loops from protein C

PDB ID 7sr9

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