title: Immucillins in custom catalytic-site cavities.
abstract: Neighboring-group participation in the reaction catalyzed by purine nucleoside phosphorylase involves a compression mode between the 5'- and 4'-ribosyl oxygens, facilitated by His257. The His257Gly mutant opens a space in the catalytic site. Hydrophobic 5'-substituted Immucillins are transition-state analogue inhibitors of this mutant enzyme. Dissociation constants as low as 2pM are achieved, with K(m)/K(d) as high as 400,000,000.
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Murkin
authors.forename: Keith
authors.initials: K
authors.lastname: Clinch
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Mason
authors.forename: Peter C
authors.initials: PC
authors.lastname: Tyler
authors.forename: Vern L
authors.initials: VL
authors.lastname: Schramm
mesh_terms: D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D005998:Glycine / Q000737:chemistry / Q000235:genetics; D006639:Histidine / Q000737:chemistry / Q000235:genetics; D006801:Humans; D007093:Imidazoles / Q000737:chemistry; D007700:Kinetics; D009154:Mutation; D011487:Protein Conformation; D011684:Purine Nucleosides / Q000737:chemistry*; D011683:Purine-Nucleoside Phosphorylase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011744:Pyrimidinones / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D007093:Imidazoles; D011684:Purine Nucleosides; D011744:Pyrimidinones; C113101:forodesine; D006639:Histidine; D011683:Purine-Nucleoside Phosphorylase; D005998:Glycine
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