title: Ligand structures of synthetic deoxa-pyranosylamines with raucaffricine and strictosidine glucosidases provide structural insights into their binding and inhibitory behaviours.
abstract: 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 Å 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.
authors.affiliation: Department of Urology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University , Hangzhou , China .
authors.forename: Liqun
authors.initials: L
authors.lastname: Xia
authors.forename: Haili
authors.initials: H
authors.lastname: Lin
authors.forename: Agata
authors.initials: A
authors.lastname: Staniek
authors.forename: Santosh
authors.initials: S
authors.lastname: Panjikar
authors.forename: Martin
authors.initials: M
authors.lastname: Ruppert
authors.forename: Petra
authors.initials: P
authors.lastname: Hilgers
authors.forename: Jörg
authors.initials: J
authors.lastname: Williardt
authors.forename: Chitra
authors.initials: C
authors.lastname: Rajendran
authors.forename: Meitian
authors.initials: M
authors.lastname: Wang
authors.forename: Heribert
authors.initials: H
authors.lastname: Warzecha
authors.forename: Volker
authors.initials: V
authors.lastname: Jäger
authors.forename: Joachim
authors.initials: J
authors.lastname: Stöckigt
mesh_terms: D001665:Binding Sites / Q000187:drug effects; D003517:Cyclopentanes / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005959:Glucosidases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D011926:Rauwolfia / Q000166:cytology / Q000201:enzymology; D013329:Structure-Activity Relationship; D013402:Sugar Alcohols / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D003517:Cyclopentanes; D008024:Ligands; D013402:Sugar Alcohols; D005959:Glucosidases; C119910:raucaffricine beta-glucosidase; C456847:strictosidine glucosidase
keywords: Crystallization; glucosidase inhibition; structure elucidation