title: [NMR screening of potential inhibitors of Citrobacter freundii methionine].
abstract: Methionine γ-lyase [EC 4.4.1.11] participates in a methionine catabolism at a number of bacteria and protozoa eukaryotes, including pathogenic microorganisms. Lack of this enzyme at mammals allows consider it as a perspective target for rational antibacterial drug design. Currently in medical practice there are no the preparations based on an inhibition of methionine γ-lyase activity. We present results of the search of potential inhibitors of the enzyme using the NMR screening techniques based on identification of compounds, which able to bind specifically to their biological target. Study included a stage of in silico virtual screening of the library of commercially available compounds and subsequent experimental selection of the leading compounds, capable to interact with enzyme. Identification of binding was carried out by means of saturation transfer difference (STD) spectroscopy and WaterLOGSY technique. At the final stage the experimental assessment of inhibiting ability of the selected compounds in the reaction of γ-elimination of L-methionine catalyzed by methionine γ-lyase was carried out. Binding constants of two leading compounds were determined using the WaterLOGSY method. The research expands structural group of potential inhibitors of methionine γ-lyase and allows approach to the design of the inhibitors with higher efficacy.
authors.forename: E A
authors.initials: EA
authors.lastname: Batuev
authors.forename: A Iu
authors.initials: AIu
authors.lastname: Lizunov
authors.forename: E A
authors.initials: EA
authors.lastname: Morozova
authors.forename: V V
authors.initials: VV
authors.lastname: Klochkov
authors.forename: N V
authors.initials: NV
authors.lastname: Anufrieva
authors.forename: T V
authors.initials: TV
authors.lastname: Demidkina
authors.forename: V I
authors.initials: VI
authors.lastname: Pol'shakov
mesh_terms: D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D013437:Carbon-Sulfur Lyases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D016971:Citrobacter freundii / Q000737:chemistry* / Q000201:enzymology; D062126:Databases, Chemical; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000737:chemistry*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D057166:High-Throughput Screening Assays; D007700:Kinetics; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008715:Methionine / Q000737:chemistry*; D062105:Molecular Docking Simulation; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D054852:Small Molecule Libraries / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014584:User-Computer Interface
chemical_list: D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D008024:Ligands; D011994:Recombinant Proteins; D054852:Small Molecule Libraries; D008715:Methionine; D013437:Carbon-Sulfur Lyases; C021558:L-methionine gamma-lyase