title: Alternative substrates selective for S-adenosylmethionine synthetases from pathogenic bacteria.
abstract: S-adenosyl-l-methionine (AdoMet) synthetase catalyzes the production of AdoMet, the major biological methyl donor and source of methylene, amino, ribosyl, and aminopropyl groups in the metabolism of all known organism. In addition to these essential functions, AdoMet can also serve as the precursor for two different families of quorum sensing molecules that trigger virulence in Gram-negative human pathogenic bacteria. The enzyme responsible for AdoMet biosynthesis has been cloned, expressed and purified from several of these infectious bacteria. AdoMet synthetase (MAT) from Neisseria meningitidis shows similar kinetic parameters to the previously characterized Escherichia coli enzyme, while the Pseudomonas aeruginosa enzyme has a decreased catalytic efficiency for its MgATP substrate. In contrast, the more distantly related MAT from Campylobacter jejuni has an altered quaternary structure and possesses a higher catalytic turnover than the more closely related family members. Methionine analogs have been examined to delineate the substrate specificity of these enzyme forms, and several alternative substrates have been identified with the potential to block quorum sensing while still serving as precursors for essential methyl donation and radical generation reactions.
authors.affiliation: Department of Chemistry, The University of Toledo, Toledo, OH 43606, United States.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Zano
authors.forename: Pravin
authors.initials: P
authors.lastname: Bhansali
authors.forename: Amarjit
authors.initials: A
authors.lastname: Luniwal
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Viola
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D016123:Campylobacter jejuni / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D007700:Kinetics; D008716:Methionine Adenosyltransferase / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D011550:Pseudomonas aeruginosa / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D012436:S-Adenosylmethionine / Q000378:metabolism; D016415:Sequence Alignment; D013379:Substrate Specificity
chemical_list: D012436:S-Adenosylmethionine; D000255:Adenosine Triphosphate; D008716:Methionine Adenosyltransferase
keywords: AdoMet synthetase; Alternative substrates; Enzyme kinetics; Pathogenic bacteria; Quorum sensing