title: Structure-based design of inhibitors of human L-xylulose reductase modelled into the active site of the enzyme.
abstract: The program GRID was used to design potential inhibitors of human L-xylulose reductase based on a model of the holoenzyme in complex with n-butyric acid. The inclusion of phosphate or carboxylate functional groups in the ligand suggested an increase in the net binding energy of the complex up to 2.8- and 4.0-fold, respectively. This study may be useful in the development of potent and specific inhibitors of the enzyme.
authors.affiliation: Department of Medicinal Chemistry, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Carbone
authors.forename: Connie
authors.initials: C
authors.lastname: Darmanin
authors.forename: Shuhei
authors.initials: S
authors.lastname: Ishikura
authors.forename: Akira
authors.initials: A
authors.lastname: Hara
authors.forename: Ossama
authors.initials: O
authors.lastname: El-Kabbani
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D020148:Butyric Acid / Q000378:metabolism; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D020035:Holoenzymes / Q000378:metabolism; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D013816:Thermodynamics
chemical_list: D004791:Enzyme Inhibitors; D020035:Holoenzymes; D020148:Butyric Acid; D013401:Sugar Alcohol Dehydrogenases; C023300:L-xylulose reductase