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1c9t

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(New page: 200px<br /><applet load="1c9t" size="450" color="white" frame="true" align="right" spinBox="true" caption="1c9t, resolution 3.3&Aring;" /> '''COMPLEX OF BDELLASTAS...)
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[[Image:1c9t.gif|left|200px]]<br /><applet load="1c9t" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1c9t, resolution 3.3&Aring;" />
 
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'''COMPLEX OF BDELLASTASIN WITH BOVINE TRYPSIN'''<br />
 
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==Overview==
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==COMPLEX OF BDELLASTASIN WITH BOVINE TRYPSIN==
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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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<StructureSection load='1c9t' size='340' side='right'caption='[[1c9t]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1c9t]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C9T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1C9T FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.3&#8491;</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=1c9t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c9t OCA], [https://pdbe.org/1c9t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1c9t RCSB], [https://www.ebi.ac.uk/pdbsum/1c9t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1c9t ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/TRY1_BOVIN TRY1_BOVIN]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c9/1c9t_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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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=1c9t ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1C9T is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis]. Active as [http://en.wikipedia.org/wiki/Trypsin Trypsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.4 3.4.21.4] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1C9T OCA].
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*[[Trypsin 3D structures|Trypsin 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10512718 10512718]
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[[Category: Bos taurus]]
[[Category: Bos taurus]]
[[Category: Hirudo medicinalis]]
[[Category: Hirudo medicinalis]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Trypsin]]
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[[Category: Auerswald E]]
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[[Category: Auerswald, E.]]
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[[Category: Bode W]]
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[[Category: Bode, W.]]
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[[Category: Huber R]]
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[[Category: Huber, R.]]
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[[Category: Moser M]]
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[[Category: Moser, M.]]
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[[Category: Parry MA]]
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[[Category: Parry, M.A.]]
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[[Category: Rester U]]
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[[Category: Rester, U.]]
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[[Category: antistasin]]
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[[Category: complex (hydrolase/inhibitor)]]
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[[Category: hydrolase]]
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[[Category: inhibitor]]
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[[Category: plasmin]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 12:17:37 2007''
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Current revision

COMPLEX OF BDELLASTASIN WITH BOVINE TRYPSIN

PDB ID 1c9t

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