TY - JOUR
T1 - Comprehensive Inhibitor Profiling Of The Proteus Mirabilis Metalloprotease Virulence Factor Zapa (Mirabilysin)
AU - Carson, Louise
AU - Cathcart, George
AU - Scott, Christopher
AU - Hollenberg, Morley D.
AU - Walker, Brian
AU - Ceri, Howard
AU - Gilmore, Brendan
PY - 2011/8
Y1 - 2011/8
N2 - 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.
AB - 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.
U2 - 10.1016/j.biochi.2011.06.030
DO - 10.1016/j.biochi.2011.06.030
M3 - Article
VL - 93
SP - 1824
EP - 1827
JO - Biochimie
JF - Biochimie
SN - 0300-9084
IS - 10
ER -