Comprehensive inhibitor profiling of the Proteus mirabilis metalloprotease virulence factor ZapA (mirabilysin).
Biochimie
; 93(10): 1824-7, 2011 Oct.
Article
em En
| MEDLINE
| ID: mdl-21762758
ABSTRACT
In this study we report for the first time the comprehensive inhibitor profiling of the Proteus mirabilis metalloprotease virulence factor ZapA (mirabilysin) using a 160 compound focused library of N-alpha mercaptoamide dipeptides, in order to map the S(1)(') and S(2)(') binding site preferences of this important enzyme. This study has revealed a preference for the aromatic residues tyrosine and tryptophan in P(1)(') and aliphatic residues in P(2)('). From this library, six compounds were identified which exhibited sub- to low-micromolar K(i) values. The most potent inactivator, SH-CO(2)-Y-V-NH(2) was capable of preventing ZapA-mediated hydrolysis of heat-denatured IgA, indicating that these inhibitors may be capable of protecting host proteins against ZapA during colonisation and infection.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteus mirabilis
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Proteínas de Bactérias
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Fatores de Virulência
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Metaloproteases
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Inibidores Enzimáticos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article