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| | {{STRUCTURE_1wo9| PDB=1wo9 | SCENE= }} | | {{STRUCTURE_1wo9| PDB=1wo9 | SCENE= }} |
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| - | '''Selective inhibition of trypsins by insect peptides: role of P6-P10 loop'''
| + | ===Selective inhibition of trypsins by insect peptides: role of P6-P10 loop=== |
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| - | ==Overview==
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| - | 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) <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).
| + | The line below this paragraph, {{ABSTRACT_PUBMED_14622007}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 14622007 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_14622007}} |
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| | ==About this Structure== | | ==About this Structure== |
| - | Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WO9 OCA]. | + | Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WO9 OCA]. |
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| | ==Reference== | | ==Reference== |
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| | [[Category: Roussel, A.]] | | [[Category: Roussel, A.]] |
| | [[Category: Hydrolase inhibitor]] | | [[Category: Hydrolase inhibitor]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 13:56:24 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 16:19:32 2008'' |
Revision as of 13:19, 28 July 2008
Template:STRUCTURE 1wo9
Selective inhibition of trypsins by insect peptides: role of P6-P10 loop
Template:ABSTRACT PUBMED 14622007
About this Structure
Full experimental information is available from OCA.
Reference
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
Page seeded by OCA on Mon Jul 28 16:19:32 2008
