This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


1c9p

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (15:38, 13 March 2024) (edit) (undo)
 
(18 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1c9p.gif|left|200px]]<br /><applet load="1c9p" size="350" color="white" frame="true" align="right" spinBox="true"
 
-
caption="1c9p, resolution 2.8&Aring;" />
 
-
'''COMPLEX OF BDELLASTASIN WITH PORCINE TRYPSIN'''<br />
 
-
==Overview==
+
==COMPLEX OF BDELLASTASIN WITH PORCINE TRYPSIN==
-
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.
+
<StructureSection load='1c9p' size='340' side='right'caption='[[1c9p]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 +
== Structural highlights ==
 +
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</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='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>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/TRYP_PIG TRYP_PIG]
 +
== 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/c9/1c9p_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=1c9p ConSurf].
 +
<div style="clear:both"></div>
-
==About this Structure==
+
==See Also==
-
1C9P is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis] and [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with <scene name='pdbligand=CA:'>CA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. 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://oca.weizmann.ac.il/oca-bin/ocashort?id=1C9P OCA].
+
*[[Trypsin 3D structures|Trypsin 3D structures]]
-
 
+
__TOC__
-
==Reference==
+
</StructureSection>
-
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]
+
[[Category: Hirudo medicinalis]]
[[Category: Hirudo medicinalis]]
-
[[Category: Protein complex]]
+
[[Category: Large Structures]]
[[Category: Sus scrofa]]
[[Category: Sus scrofa]]
-
[[Category: Trypsin]]
+
[[Category: Rester U]]
-
[[Category: Rester, U.]]
+
-
[[Category: CA]]
+
-
[[Category: antistasin]]
+
-
[[Category: complex (hydrolase/inhibitor)]]
+
-
[[Category: hydrolase]]
+
-
[[Category: inhibitor]]
+
-
[[Category: isoaspartate]]
+
-
[[Category: plasmin]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:03:53 2008''
+

Current revision

COMPLEX OF BDELLASTASIN WITH PORCINE TRYPSIN

PDB ID 1c9p

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1c9p"
Personal tools