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Synthesis and application of a photoaffinity analog of nicotinamide adenosine dinucleotide: Identification of the active sites of glutamate and lactate dehydrogenases

Thesis/Dissertation ·
OSTI ID:5475883

A photoaffinity analog of NAD{sup +} has been synthesized by chemically coupling ({sup 32}P)2-azido-AMP and NMN{sup +} to produce ({sup 32}P)nicotinamide 2-azidoadenosine dinucleotide (2-azido-NAD{sup +}). The utility of 2-azido-NAD{sup +} as an effective active-site-directed photoprobe was demonstrated using bovine liver glutamate dehydrogenase and porcine muscle lactate dehydrogenase as model enzymes. In the absence of ultraviolet light 2-azido-NAD{sup +} is a substrate for these enzymes. The specificity of active site labeling was demonstrated by photoinhibition, saturation and competition experiments. The active sites of these enzymes were identified utilizing 2-azido-NAD{sup +}. The immobilized boronate column chromatography was used to isolate the photolabeled peptides. The results demonstrate that the photoaffinity analog of NAD{sup +} has potential application as a probe to characterize NAD{sup +}binding proteins and to identify the active sites of these proteins.

Research Organization:
Kentucky Univ., Lexington, KY (United States)
OSTI ID:
5475883
Country of Publication:
United States
Language:
English