A model for glutathione binding and activation in the fosfomycin resistance protein, FosA.

ABSTRACT: The genomically encoded fosfomycin resistance protein from Pseudomonas aeruginosa (FosA(PA)) utilizes Mn(II) and K(+) to catalyze the addition of glutathione (GSH) to C1 of the antibiotic rendering it inactive. Although this protein has been structurally and kinetically characterized with respect to the substrate, fosfomycin, questions remain regarding how the enzyme binds the thiol substrate, GSH. Computational studies have revealed a potential GSH binding site in FosA(PA) that involves six electrostatic or hydrogen-bonding interactions with protein side-chains as well as six additional residues that contribute van der Waals interactions. A strategically placed tyrosine residue, Y39, appears to be involved in the ionization of GSH during catalysis. The Y39F mutant exhibits a 13-fold reduc

SUBMITTER: Rigsby RE 

PROVIDER: S-EPMC2709490 | biostudies-literature | 2007 Aug

REPOSITORIES: biostudies-literature