Proteinase inhibition using small Bowman-Birk-type structures
Genet. mol. res. (Online)
; 6(4): 846-858, 2007. ilus, tab
Article
em En
| LILACS
| ID: lil-520062
Biblioteca responsável:
BR26.1
ABSTRACT
Bowman-Birk inhibitors (BBIs) are cysteine-rich and highly cross-linked small proteins that function as specific pseudosubstrates for digestive proteinases. They typically display a "double-headed" structure containing an independent proteinase-binding loop that can bind and inhibit trypsin, chymotrypsin and elastase. In the present study, we used computational biology to study the structural characteristics and dynamics of the inhibition mechanism of the small BBI loop expressing a 35-amino acid polypeptide (ChyTB2 inhibitor) which has coding region for the mutated chymotrypsin-inhibitory site of the soybean BBI. We found that in the BBI-trypsin inhibition complex, the most important interactions are salt bridges and hydrogen bonds, whereas in the BBI-chymotrypsin inhibition complex, the most important interactions are hydrophobic. At the same time, ChyTB2 mutant structure maintained the individual functional domain structure and excellent binding/inhibiting capacities for trypsin and chymotrypsin at the same time. These results were confirmed by enzyme-linked immunosorbend assay experiments. The results showed that modeling combined with molecular dynamics is an efficient method to describe, predict and then obtain new proteinase inhibitors. For such study, however, it is necessary to start from the sequence and structure of the mutant interacting relatively strongly with both trypsin and chymotrypsin for designing the small BBI-type inhibitor against proteinases.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
LILACS
Assunto principal:
Endopeptidases
/
Modelos Moleculares
/
Inibidor da Tripsina de Soja de Bowman-Birk
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Genet. mol. res. (Online)
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA
Ano de publicação:
2007
Tipo de documento:
Article
/
Congress and conference
País de afiliação:
Brasil
País de publicação:
BR
/
BRASIL
/
BRASILE
/
BRAZIL
/
BRESIL