2O3S

Structural Basis for Formation and Hydrolysis of Calcium Messenger Cyclic ADP-ribose by Human CD38

2O3S の概要

• エントリーDOI: 10.2210/pdb2o3s/pdb
• 関連するPDBエントリー: 1YH3 2O3Q 2O3R 2O3T 2O3U
• 分子名称: ADP-ribosyl cyclase 1, CYCLIC ADENOSINE DIPHOSPHATE-RIBOSE (3 entities in total)
• 機能のキーワード: human cd38 e226g mutant, the catalytic pocket, cadpr formation and hydrolysis, substrate binding, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass type II membrane protein: P28907
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 61679.22

構造登録者

Liu, Q.,Kriksunov, I.A.,Graeff, R.,Lee, H.C.,Hao, Q. (登録日: 2006-12-01, 公開日: 2006-12-12, 最終更新日: 2024-10-16)

主引用文献

Liu, Q.,Kriksunov, I.A.,Graeff, R.,Lee, H.C.,Hao, Q.
Structural basis for formation and hydrolysis of the calcium messenger cyclic ADP-ribose by human CD38
J.Biol.Chem., 282:5853-5861, 2007

PubMed Abstract: Human CD38 is a multifunctional ectoenzyme responsible for catalyzing the conversions from nicotinamide adenine dinucleotide (NAD) to cyclic ADP-ribose (cADPR) and from cADPR to ADP-ribose (ADPR). Both cADPR and ADPR are calcium messengers that can mobilize intracellular stores and activate influx as well. In this study, we determined three crystal structures of the human CD38 enzymatic domain complexed with cADPR at 1.5-A resolution, with its analog, cyclic GDP-ribose (cGDPR) (1.68 A) and with NGD (2.1 A) a substrate analog of NAD. The results indicate that the binding of cADPR or cGDPR to the active site induces structural rearrangements in the dipeptide Glu(146)-Asp(147) by as much as 2.7 A) providing the first direct evidence of a conformational change at the active site during catalysis. In addition, Glu(226) is shown to be critical not only in catalysis but also in positioning of cADPR at the catalytic site through strong hydrogen bonding interactions. Structural details obtained from these complexes provide a step-by-step description of the catalytic processes in the synthesis and hydrolysis of cADPR.

PubMed: 17182614
DOI: 10.1074/jbc.M609093200

実験手法

X-RAY DIFFRACTION (1.5 Å)