Photodependent inhibition of bovine spleen NAD+ glycohydrolase by 8-azido carbocyclic analogs of NAD+.
Carba-NAD+ and pseudocarba-NAD+, and their 8-azidoadenosyl derivatives, were found to be good competitive inhibitors of calf spleen NAD+ glycohydrolase. The 8-azido compounds, tested as photoaffinity labels, inhibited the enzyme in a light- and time-dependent manner; this inhibition could be prevented by 3-aminopyridine adenine dinucleotide (n3PdAD+), a competitive inhibitor of NAD+ glycohydrolase. Irradiation in the presence of the [3H]-labeled 8-azido-carba-NAD+ derivative resulted in an irreversible incorporation of the radioactivity into the enzyme that could be largely prevented by addition of n3PdAD+. These results indicate that carbocyclic-analogs of NAD+ will be useful in identifying the substrate binding site of NAD+ glycohydrolase.
Muller-Steffner
H
H
Laboratoire de Chimie Bioorganique (CNRS URA 1386), Faculté de Pharmacie, Illkirch, France.
Slama
J
J
Schuber
F
F
D000345:Affinity Labels; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008027:Light; D009243:NAD / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D009244:NAD+ Nucleosidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013154:Spleen / Q000201:enzymology*
C102093:4-(7-propanoyloxycoumarinyl)methyl cAMP; C102089:8-azidoadenosyl carba-NAD+; C102090:8-azidoadenosyl pseudocarba-NAD+; D000345:Affinity Labels; D009243:NAD; C055311:carbanicotinamide adenine dinucleotide; C002098:3-aminopyridine adenine dinucleotide; D000242:Cyclic AMP; D009244:NAD+ Nucleosidase