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ADP-Ribosyl Cyclases - A Family of cADPR and NAADP Metabolizing Enzymes

Chapter

Abstract

ADP-ribosyl cyclase cyclizes NAD to produce cyclic ADP-ribose (cADPR) and releases nicotinamide in the process [1]. It is a ubiquitous enzyme widely present in animal cells [1, 2] and has even been identified in Euglena, a protozoan [4]. The first cyclase purified was from Aplysia ovotestis [1, 5]. It is a soluble protein of approximately 30 kDa. Sequence comparison reveals that CD38, a lymphocyte antigen, is a mammalian homolog [6]. CD38 is a transmembrane glycoprotein of approximately 45 kDa [7]. It catalyzes not only the synthesis of cADPR but also its hydrolysis to ADP-ribose [8, 11]. Additionally, both CD38 and the Aplysia cyclase use NADP as a substrate and catalyze the exchange of the nicotinamide group with nicotinic acid, producing nicotinic acid adenine dinucleotide phosphate (NAADP) [12]. The Aplysia cyclase has been crystallized and its structure solved [13, 14]. Current knowledge of the structures of these enzymes and the novel multiplicity of their catalytic activities are described in this chapter. Since both of their products are Ca2+ messengers, this class of enzymes is crucial in mediating Ca2+ signaling functions in cells. Some of their physiological functions have now been revealed by gene ablation and are summarised here.

Keywords

Cyclase Activity Wildtype Mouse Euglena Gracilis Active Site Pocket Nicotinic Acid Adenine Dinucleotide Phosphate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  1. 1.Department of PharmacologyUniversity of MinnesotaMinneapolisUSA

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