title: From Genome to Proteome to Elucidation of Reactions for All Eleven Known Lytic Transglycosylases from Pseudomonas aeruginosa.
abstract: An enzyme superfamily, the lytic transglycosylases (LTs), occupies the space between the two membranes of Gram-negative bacteria. LTs catalyze the non-hydrolytic cleavage of the bacterial peptidoglycan cell-wall polymer. This reaction is central to the growth of the cell wall, for excavating the cell wall for protein insertion, and for monitoring the cell wall so as to initiate resistance responses to cell-wall-acting antibiotics. The nefarious Gram-negative pathogen Pseudomonas aeruginosa encodes eleven LTs. With few exceptions, their substrates and functions are unknown. Each P. aeruginosa LT was expressed as a soluble protein and evaluated with a panel of substrates (both simple and complex mimetics of their natural substrates). Thirty-one distinct products distinguish these LTs with respect to substrate recognition, catalytic activity, and relative exolytic or endolytic ability. These properties are foundational to an understanding of the LTs as catalysts and as antibiotic targets.
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, 46556, USA.
authors.forename: Mijoon
authors.initials: M
authors.lastname: Lee
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, 46556, USA.
authors.forename: Dusan
authors.initials: D
authors.lastname: Hesek
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, 46556, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Dik
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, 46556, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Fishovitz
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, 46556, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Lastochkin
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, 46556, USA.
authors.forename: Bill
authors.initials: B
authors.lastname: Boggess
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, 46556, USA.
authors.forename: Jed F
authors.initials: JF
authors.lastname: Fisher
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, 46556, USA.
authors.forename: Shahriar
authors.initials: S
authors.lastname: Mobashery
mesh_terms: D055162:Biocatalysis; D002473:Cell Wall / Q000737:chemistry / Q000378:metabolism; D016695:Glycosyltransferases / Q000235:genetics* / Q000378:metabolism*; D008968:Molecular Conformation; D020543:Proteome / Q000235:genetics* / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000166:cytology / Q000201:enzymology*
chemical_list: D020543:Proteome; D016695:Glycosyltransferases
keywords: anhydromuramic acid; antibiotic resistance; muropeptide; sacculus; β-lactam