3F6Y

Conformational Closure of the Catalytic Site of Human CD38 Induced by Calcium

3F6Y の概要

• エントリーDOI: 10.2210/pdb3f6y/pdb
• 分子名称: ADP-ribosyl cyclase 1, CALCIUM ION (3 entities in total)
• 機能のキーワード: calcium loaded structure, active site closure, inhibitory conformation, alternative splicing, diabetes mellitus, glycoprotein, hydrolase, membrane, nad, polymorphism, receptor, signal-anchor, transmembrane
• 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: 1
• 化学式量合計: 30490.61

構造登録者

Liu, Q.,Graeff, R.,Kriksunov, I.A.,Lam, C.M.C.,Lee, H.C.,Hao, Q. (登録日: 2008-11-07, 公開日: 2008-11-18, 最終更新日: 2024-10-09)

主引用文献

Liu, Q.,Graeff, R.,Kriksunov, I.A.,Lam, C.M.C.,Lee, H.C.,Hao, Q.
Conformational Closure of the Catalytic Site of Human CD38 Induced by Calcium
Biochemistry, 47:13966-13973, 2008

PubMed Abstract: First identified on the surface of lymphoids as a type II transmembrane protein, CD38 has now been established to have dual functions not only as a receptor but also as a multifunctional enzyme,catalyzing the synthesis of and hydrolysis of a general calcium messenger molecule, cyclic ADP-ribose(cADPR). The receptorial functions of CD38 include the induction of cell adhesion, differentiation,apoptosis, and cytokine production upon antibody ligation. Here we determined the crystal structure of calcium-loaded human CD38 at 1.45 A resolution which reveals that CD38 undergoes dramatic structural changes to an inhibited conformation in the presence of calcium. The structural changes are highly localized and occur in only two regions. The first region is part of the active site and consists of residues 121-141.In the presence of calcium, W125 moves 5 A into the active site and forms hydrophobic interactions with W189. The movement closes the active site pocket and reduces entry of substrates, resulting in inhibition of the enzymatic activity. The structural role of calcium in inducing these conformational changes is readily visualized in the crystal structure. The other region that undergoes calcium-induced changes is at the receptor region, where a highly ordered helix is unraveled to a random coil. The results suggest a novel conformational coupling mechanism, whereby protein interaction targeted at the receptor region can effectively regulate the enzymatic activity of CD38.

PubMed: 19117080
DOI: 10.1021/bi801642q

実験手法

X-RAY DIFFRACTION (1.45 Å)