5BNF

Apo structure of porcine CD38

Summary for 5BNF

• Entry DOI: 10.2210/pdb5bnf/pdb
• Related: 5BNI
• Descriptor: Uncharacterized protein (2 entities in total)
• Functional Keywords: adp-hydrolase, adp-cyclase, calcium signalling, cadpr, hydrolase
• Biological source: Sus scrofa (Pig)
• Total number of polymer chains: 2
• Total formula weight: 52862.12

Authors

Ting, K.Y.,Leung, C.P.F.,Graeff, R.M.,Lee, H.C.,Hao, Q.,Kotaka, M. (deposition date: 2015-05-26, release date: 2016-05-25, Last modification date: 2024-11-13)

Primary citation

Ting, K.Y.,Leung, C.F.,Graeff, R.M.,Lee, H.C.,Hao, Q.,Kotaka, M.
Porcine CD38 exhibits prominent secondary NAD(+) cyclase activity.
Protein Sci., 25:650-661, 2016

PubMed Abstract: 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.

PubMed: 26660500
DOI: 10.1002/pro.2859

Experimental method

X-RAY DIFFRACTION (2.3 Å)