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| | ==BOVINE THROMBIN--BM12.1700 COMPLEX== | | ==BOVINE THROMBIN--BM12.1700 COMPLEX== |
| - | <StructureSection load='1uvu' size='340' side='right' caption='[[1uvu]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='1uvu' size='340' side='right'caption='[[1uvu]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1uvu]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UVU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1UVU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1uvu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UVU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UVU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DCH:3-(7-DIAMINOMETHYL-NAPHTHALEN-2-YL)-PROPIONIC+ACID+ETHYL+ESTER'>DCH</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]] 2.8Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] </span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DCH:3-(7-DIAMINOMETHYL-NAPHTHALEN-2-YL)-PROPIONIC+ACID+ETHYL+ESTER'>DCH</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1uvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uvu OCA], [http://pdbe.org/1uvu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1uvu RCSB], [http://www.ebi.ac.uk/pdbsum/1uvu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1uvu 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=1uvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uvu OCA], [https://pdbe.org/1uvu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1uvu RCSB], [https://www.ebi.ac.uk/pdbsum/1uvu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1uvu ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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). | + | [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]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/uv/1uvu_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/uv/1uvu_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <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> |
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| | ==See Also== | | ==See Also== |
| - | *[[Thrombin|Thrombin]] | + | *[[Thrombin 3D Structures|Thrombin 3D Structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Bos taurus]] | | [[Category: Bos taurus]] |
| - | [[Category: Thrombin]] | + | [[Category: Large Structures]] |
| - | [[Category: Engh, R A]] | + | [[Category: Engh RA]] |
| - | [[Category: Huber, R]] | + | [[Category: Huber R]] |
| - | [[Category: Blood coagulation]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Serine protease]]
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| Structural highlights
Function
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
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
BACKGROUND: The explosive growth in the rate of X-ray determination of protein structures is fuelled largely by the expectation that structural information will be useful for pharmacological and biotechnological applications. For example, there have been intensive efforts to develop orally administrable antithrombotic drugs using information about the crystal structures of blood coagulation factors, including thrombin. Most of the low molecular weight thrombin inhibitors studied so far are based on arginine and benzamidine. We sought to expand the database of information on thrombin-inhibitor binding by studying new classes of inhibitors. RESULTS: We report the structures of three new inhibitors complexed with thrombin, two based on 4-aminopyridine and one based on naphthamidine. We observe several geometry changes in the protein main chain and side chains which accompany inhibitor binding. The two inhibitors based on 4-aminopyridine bind in notably different ways: one forms a water-mediated hydrogen bond to the active site Ser195, the other induces a rotation of the Ser214-Trp215 peptide plane that is unprecedented in thrombin structures. These binding modes also differ in their 'weak' interactions, including CH-O hydrogen bonds and interactions between water molecules and aromatic pi-clouds. Induced-fit structural changes were also seen in the structure of the naphthamidine inhibitor complex. CONCLUSIONS: Protein flexibility and variable water structures are essential elements in protein-ligand interactions. Ligand design strategies that fail to take this into account may overlook or underestimate the potential of lead structures. Further, the significance of 'weak' interactions must be considered both in crystallographic refinement and in analysis of binding mechanisms.
Enzyme flexibility, solvent and 'weak' interactions characterize thrombin-ligand interactions: implications for drug design.,Engh RA, Brandstetter H, Sucher G, Eichinger A, Baumann U, Bode W, Huber R, Poll T, Rudolph R, von der Saal W Structure. 1996 Nov 15;4(11):1353-62. PMID:8939759[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Engh RA, Brandstetter H, Sucher G, Eichinger A, Baumann U, Bode W, Huber R, Poll T, Rudolph R, von der Saal W. Enzyme flexibility, solvent and 'weak' interactions characterize thrombin-ligand interactions: implications for drug design. Structure. 1996 Nov 15;4(11):1353-62. PMID:8939759
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