Structural basis for the inhibition of porcine pepsin by Ascaris pepsin inhibitor-3.
Nat Struct Biol
; 7(8): 653-7, 2000 Aug.
Article
en En
| MEDLINE
| ID: mdl-10932249
The three-dimensional structures of pepsin inhibitor-3 (PI-3) from Ascaris suum and of the complex between PI-3 and porcine pepsin at 1. 75 A and 2.45 A resolution, respectively, have revealed the mechanism of aspartic protease inhibition by this unique inhibitor. PI-3 has a new fold consisting of two domains, each comprising an antiparallel beta-sheet flanked by an alpha-helix. In the enzyme-inhibitor complex, the N-terminal beta-strand of PI-3 pairs with one strand of the 'active site flap' (residues 70-82) of pepsin, thus forming an eight-stranded beta-sheet that spans the two proteins. PI-3 has a novel mode of inhibition, using its N-terminal residues to occupy and therefore block the first three binding pockets in pepsin for substrate residues C-terminal to the scissile bond (S1'-S3'). The molecular structure of the pepsin-PI-3 complex suggests new avenues for the rational design of proteinaceous aspartic proteinase inhibitors.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pepstatinas
/
Porcinos
/
Proteínas
/
Pepsina A
/
Ascaris suum
Límite:
Animals
Idioma:
En
Revista:
Nat Struct Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2000
Tipo del documento:
Article
País de afiliación:
Canadá
Pais de publicación:
Estados Unidos