6533b835fe1ef96bd129f55b
RESEARCH PRODUCT
Ligand structures of synthetic deoxa-pyranosylamines with raucaffricine and strictosidine glucosidases provide structural insights into their binding and inhibitory behaviours
Heribert WarzechaSantosh PanjikarAgata StaniekMartin RuppertJoachim StöckigtHaili LinJörg WilliardtLiqun XiaPetra HilgersVolker JägerMeitian WangChitra Rajendransubject
Models MolecularStereochemistryCyclopentanesLigandsRauwolfiaStructure-Activity RelationshipSugar AlcoholsRauvolfia serpentinaDrug DiscoveryHydrolasePharmacologychemistry.chemical_classificationBinding SitesDose-Response Relationship DrugMolecular StructurebiologyAlkaloidActive siteGeneral Medicinebiology.organism_classificationLigand (biochemistry)EnzymeBiochemistrychemistryStrictosidinebiology.proteinGlucosidasesGlucosidasesdescription
Insight into the structure and inhibition mechanism of O-β-d-glucosidases by deoxa-pyranosylamine type inhibitors is provided by X-ray analysis of complexes between raucaffricine and strictosidine glucosidases and N-(cyclohexylmethyl)-, N-(cyclohexyl)- and N-(bromobenzyl)-β-d-gluco-1,5-deoxa-pyranosylamine. All inhibitors anchored exclusively in the catalytic active site by competition with appropriate enzyme substrates. Thus facilitated prospective elucidation of the binding networks with residues located at <3.9 A distance will enable the development of potent inhibitors suitable for the production of valuable alkaloid glucosides, raucaffricine and strictosidine, by means of synthesis in Rauvolfia serpentina cell suspension cultures.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-08-20 | Journal of Enzyme Inhibition and Medicinal Chemistry |