1wo9
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:1wo9.jpg|left|200px]] | + | [[Image:1wo9.jpg|left|200px]] |
| - | + | ||
| - | '''Selective inhibition of trypsins by insect peptides: role of P6-P10 loop''' | + | {{Structure |
| + | |PDB= 1wo9 |SIZE=350|CAPTION= <scene name='initialview01'>1wo9</scene> | ||
| + | |SITE= | ||
| + | |LIGAND= | ||
| + | |ACTIVITY= | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''Selective inhibition of trypsins by insect peptides: role of P6-P10 loop''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1WO9 is a [ | + | 1WO9 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WO9 OCA]. |
==Reference== | ==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:[http:// | + | 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: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Darbon, H.]] | [[Category: Darbon, H.]] | ||
| Line 19: | Line 28: | ||
[[Category: hydrolase inhibitor]] | [[Category: hydrolase inhibitor]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:59:38 2008'' |
Revision as of 12:59, 20 March 2008
| |||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Selective inhibition of trypsins by insect peptides: role of P6-P10 loop
Overview
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).
About this Structure
1WO9 is a Protein complex structure of sequences from [1]. Full crystallographic 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 Thu Mar 20 14:59:38 2008
