3edx: Difference between revisions

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<StructureSection load='3edx' size='340' side='right'caption='[[3edx]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
<StructureSection load='3edx' size='340' side='right'caption='[[3edx]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3edx]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EDX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3EDX FirstGlance]. <br>
<table><tr><td colspan='2'>[[3edx]] is a 6 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=3EDX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3EDX FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1tq0|1tq0]], [[3ee0|3ee0]]</div></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">F2, Cf2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] </span></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=3edx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3edx OCA], [https://pdbe.org/3edx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3edx RCSB], [https://www.ebi.ac.uk/pdbsum/3edx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3edx ProSAT]</span></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=3edx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3edx OCA], [https://pdbe.org/3edx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3edx RCSB], [https://www.ebi.ac.uk/pdbsum/3edx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3edx ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== 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).  
[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 ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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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=3edx ConSurf].
</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=3edx ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The thrombin mutant W215A/E217A features a drastically impaired catalytic activity toward chromogenic and natural substrates but efficiently activates the anticoagulant protein C in the presence of thrombomodulin. As the remarkable anticoagulant properties of this mutant continue to be unraveled in preclinical studies, we solved the x-ray crystal structures of its free form and its complex with the active site inhibitor H-d-Phe-Pro-Arg-CH(2)Cl (PPACK). The PPACK-bound structure of W215A/E217A is identical to the structure of the PPACK-bound slow form of thrombin. On the other hand, the structure of the free form reveals a collapse of the 215-217 strand that crushes the primary specificity pocket. The collapse results from abrogation of the stacking interaction between Phe-227 and Trp-215 and the polar interactions of Glu-217 with Thr-172 and Lys-224. Other notable changes are a rotation of the carboxylate group of Asp-189, breakage of the H-bond between the catalytic residues Ser-195 and His-57, breakage of the ion pair between Asp-222 and Arg-187, and significant disorder in the 186- and 220-loops that define the Na(+) site. These findings explain the impaired catalytic activity of W215A/E217A and demonstrate that the analysis of the molecular basis of substrate recognition by thrombin and other proteases requires crystallization of both the free and bound forms of the enzyme.
The anticoagulant thrombin mutant W215A/E217A has a collapsed primary specificity pocket.,Pineda AO, Chen ZW, Caccia S, Cantwell AM, Savvides SN, Waksman G, Mathews FS, Di Cera E J Biol Chem. 2004 Sep 17;279(38):39824-8. Epub 2004 Jul 13. PMID:15252033<ref>PMID:15252033</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3edx" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Thrombin 3D Structures|Thrombin 3D Structures]]
*[[Thrombin 3D Structures|Thrombin 3D Structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Lk3 transgenic mice]]
[[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: Cleavage on pair of basic residue]]
[[Category: Gamma-carboxyglutamic acid]]
[[Category: Glycoprotein]]
[[Category: Hydrolase]]
[[Category: Kringle]]
[[Category: Protease]]
[[Category: Serine protease]]
[[Category: Zymogen]]

Revision as of 16:01, 30 August 2023

Crystal structure of the W215A/E217A mutant of murine thrombinCrystal structure of the W215A/E217A mutant of murine thrombin

Structural highlights

3edx is a 6 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.4Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

3edx, resolution 2.40Å

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