1ycp: Difference between revisions
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==THE CRYSTAL STRUCTURE OF FIBRINOGEN-AA PEPTIDE 1-23 (F8Y) BOUND TO BOVINE THROMBIN EXPLAINS WHY THE MUTATION OF PHE-8 TO TYROSINE STRONGLY INHIBITS NORMAL CLEAVAGE AT ARGININE-16== | ==THE CRYSTAL STRUCTURE OF FIBRINOGEN-AA PEPTIDE 1-23 (F8Y) BOUND TO BOVINE THROMBIN EXPLAINS WHY THE MUTATION OF PHE-8 TO TYROSINE STRONGLY INHIBITS NORMAL CLEAVAGE AT ARGININE-16== | ||
<StructureSection load='1ycp' size='340' side='right' caption='[[1ycp]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='1ycp' size='340' side='right'caption='[[1ycp]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1ycp]] is a 7 chain structure with sequence from [ | <table><tr><td colspan='2'>[[1ycp]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YCP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YCP FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ycp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ycp OCA], [https://pdbe.org/1ycp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ycp RCSB], [https://www.ebi.ac.uk/pdbsum/1ycp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ycp ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == 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 == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/yc/1ycp_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/yc/1ycp_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/ | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </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/ | </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=1ycp ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
| Line 31: | Line 30: | ||
==See Also== | ==See Also== | ||
*[[Thrombin|Thrombin]] | *[[Thrombin 3D Structures|Thrombin 3D Structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
| Line 37: | Line 36: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Bos taurus]] | [[Category: Bos taurus]] | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Edwards BFP]] | ||
[[Category: | [[Category: Malkowski MG]] | ||
Latest revision as of 10:31, 9 October 2024
THE CRYSTAL STRUCTURE OF FIBRINOGEN-AA PEPTIDE 1-23 (F8Y) BOUND TO BOVINE THROMBIN EXPLAINS WHY THE MUTATION OF PHE-8 TO TYROSINE STRONGLY INHIBITS NORMAL CLEAVAGE AT ARGININE-16THE CRYSTAL STRUCTURE OF FIBRINOGEN-AA PEPTIDE 1-23 (F8Y) BOUND TO BOVINE THROMBIN EXPLAINS WHY THE MUTATION OF PHE-8 TO TYROSINE STRONGLY INHIBITS NORMAL CLEAVAGE AT ARGININE-16
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 PubMedA peptide containing residues 1-50 of the Aalpha-chain of fibrinogen, expressed as a fusion peptide with beta-galactosidase, is rapidly cleaved by thrombin at Arg-16, similarly to whole fibrinogen. When Phe-8, which is highly conserved, is replaced with tyrosine (F8Y), the cleavage is slowed drastically [Lord, Byrd, Hede, Wei and Colby (1990) J. Biol. Chem. 265, 838-843]. To examine the structural basis for this result, we have determined the crystal structure of bovine thrombin complexed with a synthetic peptide containing residues 1-23 of fibrinogen Aalpha and the F8Y mutation. The crystals are in space group P43212, with unit-cell dimensions of a = 88.3 A (1 A = 0.1 nm), c = 195.5 A and two complexes in the asymmetric unit. The final R factor is 0.183 for 2sigma data from 7.0 to 2.5 A resolution.There is continuous density for the five residues in the P3, P2, P1, P1' and P2' positions of the peptide (Gly-14f to Pro-18f) at the active site of thrombin, and isolated but well-defined density for Tyr-8f at position P9 in the hydrophobic pocket of thrombin. The tyrosine residue is shifted relative to phenylalanine in the native peptide because the phenol side chain is larger and makes a novel, intrapeptide hydrogen bond with Gly-14f. Adjacent peptide residues cannot form the hydrogen bonds that stabilize the secondary structure of the native peptide. Consequently, the 'reaction'geometry at the scissile bond, eight residues from the mutation, is perturbed and the peptide is mostly uncleaved in the crystal structure. Crystal structure of fibrinogen-Aalpha peptide 1-23 (F8Y) bound to bovine thrombin explains why the mutation of Phe-8 to tyrosine strongly inhibits normal cleavage at Arg-16.,Malkowski MG, Martin PD, Lord ST, Edwards BF Biochem J. 1997 Sep 15;326 ( Pt 3):815-22. PMID:9307032[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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