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Human CD38 is an authentic NAD(P)+ glycohydrolase
V Berthelier1, J M Tixier, H Muller-Steffner
1Laboratoire d'Immunologie Cellulaire, Unité Associée 625 du Centre National de la Recherche Scientifique, Groupe Hospitalier Pitié-Salpêtière, 83 boulevard de l'Hôpital, 75013 Paris, France.
The Biochemical Journal
|May 23, 1998
Summary
The leukocyte surface antigen CD38 is a NAD+ glycohydrolase, not primarily an ADP-ribosyl cyclase. This enzyme catalyzes NAD+ hydrolysis, producing ADP-ribose and nicotinamide, with cyclic ADP-ribose as a byproduct, not an intermediate.
Area of Science:
- Biochemistry
- Enzymology
- Molecular Biology
Background:
- Leukocyte surface antigen CD38 exhibits ecto-enzyme activity.
- CD38 primarily functions as a NAD+ glycohydrolase, converting NAD+ to ADP-ribose and nicotinamide.
- CD38 also possesses ADP-ribosyl cyclase and cyclic ADP-ribose hydrolase activities.
Purpose of the Study:
- To classify CD38's enzymatic role in ADP-ribosyl moiety transfer from NAD+.
- To investigate CD38's substrate specificity and kinetic mechanisms.
- To elucidate the reaction pathways and intermediates of CD38 activity.
Main Methods:
- Enzyme kinetics studies.
- Substrate specificity analysis using NAD+ and nicotinamide guanine dinucleotide.
- Investigation of reaction mechanisms and intermediate formation.
Main Results:
- CD38-catalyzed cleavage of NAD+ forms an E.ADP-ribosyl intermediate common to all pathways.
- This intermediate undergoes hydrolysis, methanolysis, transglycosidation, or intramolecular cyclization to cyclic ADP-ribose.
- Cyclic ADP-ribose is a reaction product, not an obligatory intermediate in CD38's glycohydrolase activity.
- Nicotinamide guanine dinucleotide as a substrate favors cyclization.
Conclusions:
- CD38 functions as a classical NAD(P)+ glycohydrolase (EC 3.2.2.6).
- The prevailing model of CD38 acting sequentially as an ADP-ribosyl cyclase then hydrolase is not supported.
- Cyclic ADP-ribose is a byproduct, not a mandatory intermediate in the primary hydrolytic function of CD38.