5BNI

Porcine CD38 complexed with complexed with a covalent intermediate, ribo-F-ribose-5'-phosphate

5BNI の概要

• エントリーDOI: 10.2210/pdb5bni/pdb
• 関連するPDBエントリー: 5BNF
• 分子名称: Uncharacterized protein, [(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl [(2R,3R,4S)-4-fluoro-3-hydroxytetrahydrofuran-2-yl]methyl dihydrogen diphosphate (3 entities in total)
• 機能のキーワード: covalent complex, adp-ribosyl cyclase, cd38, calcium signalling, hydrolase
• 由来する生物種: Sus scrofa (Pig)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 53407.43

構造登録者

Ting, K.Y.,Leung, C.F.P.,Graeff, R.M.,Lee, H.C.,Hao, Q.,Kotaka, M. (登録日: 2015-05-26, 公開日: 2016-05-25)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.5 Å)