|Title||Substrate-assisted leaving group activation in enzyme-catalyzed N-glycosidic bond cleavage.|
|Publication Type||Journal Article|
|Year of Publication||2005|
|Authors||Loverix, S., P. Geerlings, M. McNaughton, K. Augustyns, A. Vandemeulebroucke, J. Steyaert, and W. Versées|
|Journal||J Biol Chem|
|Date Published||2005 Apr 15|
|Keywords||Animals, Catalysis, Glycosides, Hydrogen Bonding, Hydrogen-Ion Concentration, Ions, Kinetics, Models, Chemical, Models, Molecular, Mutagenesis, Oxygen, Protein Binding, Protein Conformation, Purines, Substrate Specificity, Trypanosoma vivax, Tryptophan|
In enzymatic depurination of nucleosides, the 5'-OH group of the ribose moiety of the substrate is often shown to contribute substantially to catalysis. The purine-specific nucleoside hydrolase from Trypanosoma vivax (TvNH) fixes the 5'-OH group in a gauche,trans orientation about the C4'-C5' bond, enabling the 5'-oxygen to accept an intramolecular hydrogen bond from the C8-atom of the purine leaving group. High level ab initio quantum chemical calculations indicate that this interaction promotes protonation of the purine at N7. Steady state kinetics comprising engineered substrates confirm that a considerable fraction of the catalytic 5'-OH effect can be attributed to leaving group activation.
|Alternate Journal||J. Biol. Chem.|
Substrate-assisted leaving group activation in enzyme-catalyzed N-glycosidic bond cleavage.