title: A micromolar O-sulfated thiohydroximate inhibitor bound to plant myrosinase.
abstract: The 1.6 A resolution structure of the micromolar competitive inhibitor S-(N,N-dimethylaminoethyl) phenylacetothiohydroximate-O-sulfate bound to Sinapis alba myrosinase, a plant thioglucosidase, is reported. Myrosinase and its substrates, the glucosinolates, are part of the plant's defence system. The sulfate group and the phenyl group of the inhibitor bind to the aglycon-binding site of the enzyme, whereas the N,N-dimethyl group binds to the glucose-binding site and explains the large improvement in binding affinity compared with previous compounds. The structure suggests ways to increase the potency and specificity of the compound by improving the interactions with the hydrophobic pocket of the aglycon-binding site.
authors.affiliation: UJF-EMBL-CNRS UMI 3265, Unit of Virus Host Cell Interactions, BP 181, France.
authors.forename: Arthur
authors.initials: A
authors.lastname: Besle
authors.forename: Xavier
authors.initials: X
authors.lastname: Brazzolotto
authors.forename: Arnaud
authors.initials: A
authors.lastname: Tatibouët
authors.forename: Deimante
authors.initials: D
authors.lastname: Cerniauskaite
authors.forename: Estelle
authors.initials: E
authors.lastname: Gallienne
authors.forename: Patrick
authors.initials: P
authors.lastname: Rollin
authors.forename: Wim P
authors.initials: WP
authors.lastname: Burmeister
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D010091:Oximes / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D031226:Sinapis / Q000201:enzymology*; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013463:Sulfuric Acid Esters / Q000737:chemistry* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D010091:Oximes; D013438:Sulfhydryl Compounds; D013463:Sulfuric Acid Esters; D006026:Glycoside Hydrolases; C022739:thioglucosidase