1wo9: Difference between revisions
No edit summary |
No edit summary |
||
| 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
| |||||||||||||
| 1wo9 | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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
