A micromolar O-sulfated thiohydroximate inhibitor bound to plant myrosinase.
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.
Besle
Arthur
A
UJF-EMBL-CNRS UMI 3265, Unit of Virus Host Cell Interactions, BP 181, France.
Brazzolotto
Xavier
X
Tatibouët
Arnaud
A
Cerniauskaite
Deimante
D
Gallienne
Estelle
E
Rollin
Patrick
P
Burmeister
Wim P
WP
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
D004791:Enzyme Inhibitors; D010091:Oximes; D013438:Sulfhydryl Compounds; D013463:Sulfuric Acid Esters; D006026:Glycoside Hydrolases; C022739:thioglucosidase