Comprehensive Inhibitor Profiling Of The Proteus Mirabilis Metalloprotease Virulence Factor Zapa (Mirabilysin)

Louise Carson, George Cathcart, Christopher Scott, Morley D. Hollenberg, Brian Walker, Howard Ceri, Brendan Gilmore

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 S1´ and S2´ binding site preferences of this important enzyme. This study has revealed a preference for the aromatic residues tyrosine and tryptophan in P1´ and aliphatic residues in P2´. From this library, six compounds were identified which exhibited sub- to low micromolar Ki values. The most potent inactivator, SH-CO2-Y-V-NH2 was capable of preventing ZapA-mediated hydrolysis of heat denatured IgA, indicating these inhibitors may be capable of protecting host proteins against ZapA during colonisation and infection.
Original languageEnglish
Pages (from-to)1824-1827
Number of pages4
JournalBiochimie
Volume93
Issue number10
DOIs
Publication statusPublished - Aug 2011

ASJC Scopus subject areas

  • Biochemistry

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