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Substrate-assisted leaving group activation in enzyme-catalyzed N-glycosidic bond cleavage

Publication Type:

Journal Article

Authors:

Loverix,S.; Geerlings,P.; McNaughton,M.; Augustyns,K.; Vandemeulebroucke,A.; Steyaert,J.; Versees,W.

Source:

J. Biol. Chem, Volume 280, Issue 15, p.14799 - 14802 (2005)

URL:

PM:15695817

Keywords:

Animals; Catalysis; chemistry; enzymology; Glycosides; Hydrogen Bonding; Hydrogen-Ion Concentration; Ions; Kinetics; Models; Chemical; Models; Molecular; mutagenesis; Oxygen; Protein Binding; Protein Conformation; Purines; Substrate Specificity; Trypanosoma

Abstract:

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

Notes:

DA - 20050411
IS - 0021-9258 (Print)
LA - eng
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
RN - 0 (Glycosides)
RN - 0 (Ions)
RN - 0 (Purines)
RN - 73-22-3 (Tryptophan)
RN - 7782-44-7 (Oxygen)
SB - IM