title: Structural insight into the interaction of O-acetylserine sulfhydrylase with competitive, peptidic inhibitors by saturation transfer difference-NMR.
abstract: O-acetylserine sulfhydrylase (OASS), the enzyme catalysing the last step of cysteine biosynthesis in bacteria, is involved in antibiotic resistance and biofilm formation. Since mammals lack OASS, it is a potential target for antimicrobials. However, a limited number of inhibitors has been developed and crystallized in complex with OASS. STD-NMR was applied to study the interaction of the inhibitory pentapeptide MNYDI with the CysK and CysM OASS isozymes from Salmonella Typhimurium. Results are in excellent agreement with docking and SAR studies and confirm the important role played by the C-terminal Ile5 and the arylic moiety at P3 in dictating affinity.
authors.affiliation: Department of Neurosciences, University of Parma, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Benoni
authors.affiliation: Department of Oncology and Advanced Techniques, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy.
authors.forename: Thelma A
authors.initials: TA
authors.lastname: Pertinhez
authors.affiliation: Department of Food Sciences, University of Parma, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Spyrakis
authors.affiliation: Aptuit, Medicine Research Center, Verona, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Davalli
authors.affiliation: Department of Pharmaceutical Sciences, Section of General and Organic Chemistry 'A. Marchesini', University of Milan, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Pellegrino
authors.affiliation: Department of Pharmacy, University of Parma, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Paredi
authors.affiliation: Department of Pharmacy, University of Parma, Italy.
authors.forename: Angelica
authors.initials: A
authors.lastname: Pezzotti
authors.affiliation: Department of Neurosciences, University of Parma, Italy.|National Institute for Biostructures and Biosystems, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Bettati
authors.affiliation: Department of Pharmacy, University of Parma, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Campanini
authors.affiliation: Department of Pharmacy, University of Parma, Italy.|National Institute for Biostructures and Biosystems, Rome, Italy.|Institute of Biophysics, CNR, Pisa, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mozzarelli
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D003547:Cysteine Synthase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D018604:Epitope Mapping; D006193:Haemophilus influenzae / Q000201:enzymology; D006860:Hydrogen Bonding; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D019151:Peptide Library; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012486:Salmonella typhimurium / Q000201:enzymology*; D040681:Structural Homology, Protein
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D009842:Oligopeptides; D019151:Peptide Library; D011994:Recombinant Proteins; C000610120:methionyl-asparagyl-tyrosyl-aspartyl-isoleucine; D003547:Cysteine Synthase
keywords: Saturation Transfer Difference NMR; cysteine biosynthesis; cysteine synthase