title: Reactions of the three AmpD enzymes of Pseudomonas aeruginosa.
abstract: A group of Gram-negative bacteria, including the problematic pathogen Pseudomonas aeruginosa, has linked the steps in cell-wall recycling with the ability to manifest resistance to β-lactam antibiotics. A key step at the crossroads of the two events is performed by the protease AmpD, which hydrolyzes the peptide in the metabolite that influences these events. In contrast to other organisms that harbor this elaborate system, the genomic sequences of P. aeruginosa reveal it to have three paralogous genes for this protease, designated as ampD, ampDh2, and ampDh3. The recombinant gene products were purified to homogeneity, and their functions were assessed by the use of synthetic samples of three bacterial metabolites in cell-wall recycling and of three surrogates of cell-wall peptidoglycan. The results unequivocally identify AmpD as the bona fide recycling enzyme and AmpDh2 and AmpDh3 as enzymes involved in turnover of the bacterial cell wall itself. These findings define for the first time the events mediated by these three enzymes that lead to turnover of a key cell-wall recycling metabolite as well as the cell wall itself in its maturation.
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame , Notre Dame, Indiana 46556, United States.
authors.forename: Weilie
authors.initials: W
authors.lastname: Zhang
authors.forename: Mijoon
authors.initials: M
authors.lastname: Lee
authors.forename: Dusan
authors.initials: D
authors.lastname: Hesek
authors.forename: Elena
authors.initials: E
authors.lastname: Lastochkin
authors.forename: Bill
authors.initials: B
authors.lastname: Boggess
authors.forename: Shahriar
authors.initials: S
authors.lastname: Mobashery
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D045726:Metalloproteases / Q000737:chemistry* / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000201:enzymology*; D037521:Virulence Factors / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors; C586328:AmpDh2 protein, Pseudomonas aeruginosa; D045726:Metalloproteases