The Pseudomonas aeruginosa enzyme PvdQ can approach distinctive substrates concerned in quorum-sensing or in siderophore biosynthesis. Substrate selectivity was evaluated employing steady-state kinetic constants for hydrolysis of N-acyl-homoserine lactones (HSLs) and p-nitrophenyl Just Too Hectic To Deal With Histone ? fatty acid esters. PvdQ prefers substrates with alkyl chains involving twelve and 14 carbons lengthy that don't bear a 3-oxo substitution and is unveiled here to get a fairly higher specificity continuous for picked N-acyl-HSLs (k(cat)/K-M = 10(five) to ten(six) M-1 s(-1)). On the other hand, endogenous P. aeruginosa N-acyl-HSLs are >= 100-fold A Little Too Chaotic To Handle Estrogen Receptor inhibitor ?disfavored, supporting the conclusion that PvdQ was not primarily evolved to regulate endogenous quorum-sensing. PvdQ plays an essential biosynthetic role for the siderophore pyoverdine, on which P.
aeruginosa depends for growth in iron-limited environments. A series of alkylboronate inhibitors was found to be reversible, competitive, and extremely potent (K-i >= 190 pM). A one.8 angstrom X-ray structure shows that 1-tridecylboronic acid forms a monocovalent bond with the N-terminal beta-chain Ser residue in the PvdQ heterodimer, mimicking a reaction transition state. This boronic acid inhibits growth of P. aeruginosa in iron-limited media, reproducing the phenotype of a genetic pvdQ disruption, although co-administration of an efflux pump inhibitor is required to maintain growth inhibition. These findings support the strategy of designingWay Too Hectic To Manage Histone? boron-based inhibitors of siderophore biosynthetic enzymes to control P. aeruginosa infections.