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| <StructureSection load='1c9p' size='340' side='right'caption='[[1c9p]], [[Resolution|resolution]] 2.80Å' scene=''> | | <StructureSection load='1c9p' size='340' side='right'caption='[[1c9p]], [[Resolution|resolution]] 2.80Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[1c9p]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Hirme Hirme] and [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C9P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1C9P FirstGlance]. <br> | | <table><tr><td colspan='2'>[[1c9p]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis] and [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C9P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1C9P FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</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='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=IAS:BETA-L-ASPARTIC+ACID'>IAS</scene></td></tr> | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=IAS:BETA-L-ASPARTIC+ACID'>IAS</scene></td></tr> |
| <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Trypsin Trypsin], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.4 3.4.21.4] </span></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=1c9p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c9p OCA], [https://pdbe.org/1c9p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1c9p RCSB], [https://www.ebi.ac.uk/pdbsum/1c9p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1c9p 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=1c9p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c9p OCA], [https://pdbe.org/1c9p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1c9p RCSB], [https://www.ebi.ac.uk/pdbsum/1c9p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1c9p ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function == | | == Function == |
| [[https://www.uniprot.org/uniprot/BDEL_HIRME BDEL_HIRME]] Strong inhibitor of mammalian trypsin, plasmin and acrosin.
| | [https://www.uniprot.org/uniprot/TRYP_PIG TRYP_PIG] |
| == 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=1c9p 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=1c9p ConSurf]. |
| <div style="clear:both"></div> | | <div style="clear:both"></div> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| The serine proteinase plasmin is, together with tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA), involved in the dissolution of blood clots in a fibrin-dependent manner. Moreover, plasmin plays a key role in a variety of other activation cascades such as the activation of metalloproteinases, and has also been implicated in wound healing, pathogen invasion, cancer invasion and metastasis. The leech-derived (Hirudo medicinalis) antistasin-type inhibitor bdellastasin represents a specific inhibitor of trypsin and plasmin and thus offers a unique opportunity to evaluate the concept of plasmin inhibition. The complexes formed between bdellastasin and bovine as well as porcine beta-trypsin have been crystallised in a monoclinic and a tetragonal crystal form, containing six molecules and one molecule per asymmetric unit, respectively. Both structures have been solved and refined to 3.3 A and 2.8 A resolution. Bdellastasin turns out to have an antistasin-like fold exhibiting a bis-domainal structure like the tissue kallikrein inhibitor hirustasin. The interaction between bdellastasin and trypsin is restricted to the C-terminal subdomain of bdellastasin, particularly to its primary binding loop, comprising residues Asp30-Glu38. The reactive site of bdellastasin differs from other antistasin-type inhibitors of trypsin-like proteinases, exhibiting a lysine residue instead of an arginine residue at P1. A model of the bdellastasin-microplasmin complex has been created based on the X-ray structures. Our modelling studies indicate that both trypsin and microplasmin recognise bdellastasin by interactions which are characteristic for canonically binding proteinase inhibitors. On the basis of our three-dimensional structures, and in comparison with the tissue-kallikrein-bound and free hirustasin and the antistasin structures, we postulate that the binding of the inhibitors toward trypsin and plasmin is accompanied by a switch of the primary binding loop segment P5-P3. Moreover, in the factor Xa inhibitor antistasin, the core of the molecule would prevent an equivalent rotation of the P3 residue, making exosite interactions of antistasin with factor Xa imperative. Furthermore, Arg32 of antistasin would clash with Arg175 of plasmin, thus impairing a favourable antistasin-plasmin interaction and explaining its specificity.
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| Structure of the complex of the antistasin-type inhibitor bdellastasin with trypsin and modelling of the bdellastasin-microplasmin system.,Rester U, Bode W, Moser M, Parry MA, Huber R, Auerswald E J Mol Biol. 1999 Oct 15;293(1):93-106. PMID:10512718<ref>PMID:10512718</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 1c9p" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
| *[[Trypsin 3D structures|Trypsin 3D structures]] | | *[[Trypsin 3D structures|Trypsin 3D structures]] |
| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Hirme]] | | [[Category: Hirudo medicinalis]] |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Sus scrofa]] | | [[Category: Sus scrofa]] |
| [[Category: Trypsin]]
| | [[Category: Rester U]] |
| [[Category: Rester, U]] | |
| [[Category: Antistasin]]
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| [[Category: Hydrolase]]
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| [[Category: Hydrolase-hydrolase inhibitor complex]]
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| [[Category: Inhibitor]]
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| [[Category: Isoaspartate]]
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| [[Category: Plasmin]]
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