A mechanism of efficient G6PD inhibition by a molecular clip.
Triple duty: A synthetic molecular clip traps nicotinamide adenine dinucleotide phosphate (NADP(+); see picture) as well as occupying both the cofactor- and the substrate-binding site in glucose-6-phosphate (G6P) dehydrogenase. This combination of two inhibition mechanisms makes the clip highly effective and selective for this enzyme over other dehydrogenases.
Kirsch
Michael
M
Institut für Physiologische Chemie, Iniversitätsklinikum Essen, Hufelandstrasse 55, 45122 Essen, Germany.
Talbiersky
Peter
P
Polkowska
Jolanta
J
Bastkowski
Frank
F
Schaller
Torsten
T
de Groot
Herbert
H
Klärner
Frank-Gerrit
FG
Schrader
Thomas
T
D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D003687:Dehydroepiandrosterone / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry*; D005954:Glucosephosphate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009249:NADP / Q000378:metabolism*; D011487:Protein Conformation; D013379:Substrate Specificity; D013816:Thermodynamics
D004791:Enzyme Inhibitors; D003687:Dehydroepiandrosterone; D009249:NADP; D005954:Glucosephosphate Dehydrogenase