1wo9: Difference between revisions

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[[Image:1wo9.png|left|200px]]


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==Selective inhibition of trypsins by insect peptides: role of P6-P10 loop==
The line below this paragraph, containing "STRUCTURE_1wo9", creates the "Structure Box" on the page.
<StructureSection load='1wo9' size='340' side='right'caption='[[1wo9]]' scene=''>
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== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[1wo9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Locusta_migratoria_migratorioides Locusta migratoria migratorioides]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WO9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WO9 FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 1 model</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=1wo9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wo9 OCA], [https://pdbe.org/1wo9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1wo9 RCSB], [https://www.ebi.ac.uk/pdbsum/1wo9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1wo9 ProSAT]</span></td></tr>
{{STRUCTURE_1wo9|  PDB=1wo9  |  SCENE=  }}
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q8WQ22_LOCMI Q8WQ22_LOCMI]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
PMP-D2 and HI, two peptides from Locusta migratoria, were shown to belong to the family of tight-binding protease inhibitors. However, they interact weakly with bovine trypsin (K(i) around 100 nM) despite a trypsin-specific Arg at the primary specificity site P1. Here we demonstrate that they are potent inhibitors of midgut trypsins isolated from the same insect and of a fungal trypsin from Fusarium oxysporum (K(i) &lt;or= 0.02 nM). Therefore, they display a selectivity not existing for the parent chymotrypsin inhibitor PMP-C. By NMR, we demonstrate that HI possesses a highly rigid structure similar to the crystal structure of a variant of PMP-D2 in complex with bovine alpha-chymotrypsin. The main difference with PMP-C is located in the region from residues 20 to 24 (positions P6-P10) that interacts with the loop containing Gly173 in chymotrypsin. The corresponding residue in mammalian trypsins is always a proline that may generate a steric clash with the inhibitor. The residues thought to confer selectivity were mutated with PMP-C as a model. The resulting analogue PMP-D2(K10W,P21A,W25A) loses some activity toward insect and fungal trypsins but is a more potent inhibitor of mammalian trypsins, corresponding to a decrease of selectivity. This work represents a first attempt in tuning the selectivity of natural peptidic serine protease inhibitors by mutating residues out of the reactive loop (P3-P'3).


===Selective inhibition of trypsins by insect peptides: role of P6-P10 loop===
Selective inhibition of trypsins by insect peptides: role of P6-P10 loop.,Kellenberger C, Ferrat G, Leone P, Darbon H, Roussel A Biochemistry. 2003 Nov 25;42(46):13605-12. PMID:14622007<ref>PMID:14622007</ref>


 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
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<references/>
{{ABSTRACT_PUBMED_14622007}}
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</StructureSection>
==About this Structure==
[[Category: Large Structures]]
Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WO9 OCA].
[[Category: Locusta migratoria migratorioides]]
 
[[Category: Darbon H]]
==Reference==
[[Category: Ferrat G]]
Selective inhibition of trypsins by insect peptides: role of P6-P10 loop., Kellenberger C, Ferrat G, Leone P, Darbon H, Roussel A, Biochemistry. 2003 Nov 25;42(46):13605-12. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14622007 14622007]
[[Category: Kellenberger C]]
[[Category: Darbon, H.]]
[[Category: Leone P]]
[[Category: Ferrat, G.]]
[[Category: Roussel A]]
[[Category: Kellenberger, C.]]
[[Category: Leone, P.]]
[[Category: Roussel, A.]]
[[Category: Hydrolase inhibitor]]
 
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