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==THE CO-CRYSTAL STRUCTURE OF UNLIGANDED BOVINE ALPHA-THROMBIN AND PRETHROMBIN-2: MOVEMENT OF THE YPPW SEGMENT AND ACTIVE SITE RESIDUES UPON LIGAND BINDING== | |||
<StructureSection load='1mkx' size='340' side='right'caption='[[1mkx]], [[Resolution|resolution]] 2.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1mkx]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. The January 2002 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Thrombin'' by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2002_1 10.2210/rcsb_pdb/mom_2002_1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MKX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MKX FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</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=1mkx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mkx OCA], [https://pdbe.org/1mkx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mkx RCSB], [https://www.ebi.ac.uk/pdbsum/1mkx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mkx ProSAT]</span></td></tr> | ||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/THRB_BOVIN THRB_BOVIN] 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/mk/1mkx_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=1mkx ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Unliganded bovine alpha-thrombin and prethrombin-2 have been co-crystallized, in space group P21212, using either ammonium sulfate or polyethylene glycol 2000 (PEG2K), and their structures determined at 2.2 A and 2.3 A, respectively. Initial phases were determined by molecular replacement and refined using XPLOR to final R factors of 0.187 (Rfree = 0.255) and 0.190 (Rfree = 0.282) for the salt and PEG2K models, respectively. The apo-enzyme form of bovine alpha-thrombin shows dramatic shifts in placement for the Tyr-Pro-Pro-Trp segment, for Glu-192, and for the catalytic residues His-57 and Ser-195, when compared to 4 thrombin complexes representing different states of catalysis, namely (1) the Michaelis complex (residues 7-19 of fibrinogen A alpha with a non-cleavable scissile bond), (2) enzyme-inhibitor complex (D-Phe-Pro-Arg chloromethylketone), (3) enzyme product complex (residues 7-16 of fibrinopeptide A), and (4) the exosite complex (residues 53-64 of hirudin). The structures of bovine and human prethrombin-2 are generally similar to one another (RMS deviation of 0.68 A) but differ significantly in the Arg-15/Ile-16 cleavage region and in the three activation domains, which are disordered in bovine prethrombin-2, analogous to that seen for trypsinogen. | |||
The co-crystal structure of unliganded bovine alpha-thrombin and prethrombin-2: movement of the Tyr-Pro-Pro-Trp segment and active site residues upon ligand binding.,Malkowski MG, Martin PD, Guzik JC, Edwards BF Protein Sci. 1997 Jul;6(7):1438-48. PMID:9232645<ref>PMID:9232645</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1mkx" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Thrombin 3D Structures|Thrombin 3D Structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
[[Category: Bos taurus]] | [[Category: Bos taurus]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: RCSB PDB Molecule of the Month]] | |||
[[Category: Thrombin]] | [[Category: Thrombin]] | ||
[[Category: Edwards | [[Category: Edwards BFP]] | ||
[[Category: Malkowski | [[Category: Malkowski MG]] | ||
Latest revision as of 10:30, 23 October 2024
THE CO-CRYSTAL STRUCTURE OF UNLIGANDED BOVINE ALPHA-THROMBIN AND PRETHROMBIN-2: MOVEMENT OF THE YPPW SEGMENT AND ACTIVE SITE RESIDUES UPON LIGAND BINDINGTHE CO-CRYSTAL STRUCTURE OF UNLIGANDED BOVINE ALPHA-THROMBIN AND PRETHROMBIN-2: MOVEMENT OF THE YPPW SEGMENT AND ACTIVE SITE RESIDUES UPON LIGAND BINDING
Structural highlights
FunctionTHRB_BOVIN 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. Publication Abstract from PubMedUnliganded bovine alpha-thrombin and prethrombin-2 have been co-crystallized, in space group P21212, using either ammonium sulfate or polyethylene glycol 2000 (PEG2K), and their structures determined at 2.2 A and 2.3 A, respectively. Initial phases were determined by molecular replacement and refined using XPLOR to final R factors of 0.187 (Rfree = 0.255) and 0.190 (Rfree = 0.282) for the salt and PEG2K models, respectively. The apo-enzyme form of bovine alpha-thrombin shows dramatic shifts in placement for the Tyr-Pro-Pro-Trp segment, for Glu-192, and for the catalytic residues His-57 and Ser-195, when compared to 4 thrombin complexes representing different states of catalysis, namely (1) the Michaelis complex (residues 7-19 of fibrinogen A alpha with a non-cleavable scissile bond), (2) enzyme-inhibitor complex (D-Phe-Pro-Arg chloromethylketone), (3) enzyme product complex (residues 7-16 of fibrinopeptide A), and (4) the exosite complex (residues 53-64 of hirudin). The structures of bovine and human prethrombin-2 are generally similar to one another (RMS deviation of 0.68 A) but differ significantly in the Arg-15/Ile-16 cleavage region and in the three activation domains, which are disordered in bovine prethrombin-2, analogous to that seen for trypsinogen. The co-crystal structure of unliganded bovine alpha-thrombin and prethrombin-2: movement of the Tyr-Pro-Pro-Trp segment and active site residues upon ligand binding.,Malkowski MG, Martin PD, Guzik JC, Edwards BF Protein Sci. 1997 Jul;6(7):1438-48. PMID:9232645[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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