title: Cyclopropane-1,2-dicarboxylic acids as new tools for the biophysical investigation of O-acetylserine sulfhydrylases by fluorimetric methods and saturation transfer difference (STD) NMR.
abstract: Cysteine is a building block for many biomolecules that are crucial for living organisms. O-Acetylserine sulfhydrylase (OASS), present in bacteria and plants but absent in mammals, catalyzes the last step of cysteine biosynthesis. This enzyme has been deeply investigated because, beside the biosynthesis of cysteine, it exerts a series of "moonlighting" activities in bacteria. We have previously reported a series of molecules capable of inhibiting Salmonella typhimurium (S. typhymurium) OASS isoforms at nanomolar concentrations, using a combination of computational and spectroscopic approaches. The cyclopropane-1,2-dicarboxylic acids presented herein provide further insights into the binding mode of small molecules to OASS enzymes. Saturation transfer difference NMR (STD-NMR) was used to characterize the molecule/enzyme interactions for both OASS-A and B. Most of the compounds induce a several fold increase in fluorescence emission of the pyridoxal 5'-phosphate (PLP) coenzyme upon binding to either OASS-A or OASS-B, making these compounds excellent tools for the development of competition-binding experiments.
authors: a Department of Pharmacy , and.
authors: Giannamaria
authors: G
authors: Annunziato
authors: a Department of Pharmacy , and.
authors: Marco
authors: M
authors: Pieroni
authors: d Department of Neurosciences , University of Parma , Parma , Italy.
authors: Roberto
authors: R
authors: Benoni
authors: a Department of Pharmacy , and.
authors: Barbara
authors: B
authors: Campanini
authors: b Department of Biochemical , Biotechnological and Translational Sciences, University of Parma , Parma , Italy.|c Transfusion Medicine Unit , ASMN-IRCCS, Reggio , Emilia , Italy.
authors: Thelma A
authors: TA
authors: Pertinhez
authors: a Department of Pharmacy , and.
authors: Chiara
authors: C
authors: Pecchini
authors: a Department of Pharmacy , and.
authors: Agostino
authors: A
authors: Bruno
authors: a Department of Pharmacy , and.
authors: Joana
authors: J
authors: Magalhães
authors: e National Institute of Biostructures and Biosystems , Rome , Italy , and.
authors: Stefano
authors: S
authors: Bettati
authors: a Department of Pharmacy , and.
authors: Nina
authors: N
authors: Franko
authors: a Department of Pharmacy , and.|e National Institute of Biostructures and Biosystems , Rome , Italy , and.|f Institute of Biophysics, CNR , Pisa , Italy.
authors: Andrea
authors: A
authors: Mozzarelli
authors: a Department of Pharmacy , and.
authors: Gabriele
authors: G
authors: Costantino
mesh_terms: D003521:Cyclopropanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003547:Cysteine Synthase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D003998:Dicarboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005470:Fluorometry; D009682:Magnetic Resonance Spectroscopy; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D003521:Cyclopropanes; D003998:Dicarboxylic Acids; D004791:Enzyme Inhibitors; C000614256:cyclopropane-1,2-dicarboxylic acid; D003547:Cysteine Synthase
keywords: O-Acetylserine sulfhydrylase; cyclopropane-1,2-dicarboxylic acids; cysteine biosynthesis; drug resistance; saturation transfer difference-NMR