Porcine CD38 exhibits prominent secondary NAD+ cyclase activity

Kai Yiu Ting, Christina F P Leung, Richard M. Graeff, Hon Cheung Lee, Quan Hao, Masayo Kotaka

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5 Scopus citations


Cyclic ADP-ribose (cADPR) mobilizes intracellular Ca2+ stores and activates Ca2+ 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.

Original languageEnglish (US)
Pages (from-to)650-661
Number of pages12
JournalProtein Science
Issue number3
StatePublished - Mar 2016

Bibliographical note

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© 2015 The Protein Society.


  • CD38
  • NAD cyclization
  • X-ray crystallography
  • cyclic ADP-ribose
  • secondary enzyme activity


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