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Porcine CD 38 exhibits prominent secondary NAD + cyclase activity
Author(s) -
Ting Kai Yiu,
Leung Christina F. P.,
Graeff Richard M.,
Lee Hon Cheung,
Hao Quan,
Kotaka Masayo
Publication year - 2016
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.2859
Subject(s) - nad+ kinase , chemistry , cyclase , physics , enzyme , microbiology and biotechnology , biochemistry , biology
Cyclic ADP‐ribose (cADPR) mobilizes intracellular Ca 2+ stores and activates Ca 2+ influx to regulate a wide range of physiological processes. It is one of the products produced from the catalysis of NAD + by the multifunctional CD38/ADP‐ribosyl cyclase superfamily. After elimination of the nicotinamide ring by the enzyme, the reaction intermediate of NAD + can either be hydrolyzed to form linear ADPR or cyclized to form cADPR. We have previously shown that human CD38 exhibits a higher preference towards the hydrolysis of NAD + to form linear ADPR while Aplysia ADP‐ribosyl cyclase prefers cyclizing NAD + to form cADPR. In this study, we characterized the enzymatic properties of porcine CD38 and revealed that it has a prominent secondary NAD + cyclase activity producing cADPR. We also determined the X‐ray crystallographic structures of porcine CD38 and were able to observe conformational flexibility at the base of the active site of the enzyme which allow the NAD + reaction intermediate to adopt conformations resulting in both hydrolysis and cyclization forming linear ADPR and cADPR respectively.