3ZWO

Crystal structure of ADP ribosyl cyclase complexed with reaction intermediate

3ZWO の概要

• エントリーDOI: 10.2210/pdb3zwo/pdb
• 関連するPDBエントリー: 1LBE 1R0S 1R12 1R15 1R16 3ZWM 3ZWN 3ZWP 3ZWV 3ZWW 3ZWX 3ZWY
• 分子名称: ADP-RIBOSYL CYCLASE, GUANOSINE DIPHOSPHATE RIBOSE, 3-(AMINOCARBONYL)-1-[(2R,3R,4S,5R)-5-({[(S)-{[(S)-{[(2R,3S,4R,5R)-5-(2-AMINO-6-OXO-1,6-DIHYDRO-9H-PURIN-9-YL)-3,4-DIHYD ROXYTETRAHYDROFURAN-2-YL]METHOXY}(HYDROXY)PHOSPHORYL]OXY}(HYDROXY)PHOSPHORYL]OXY}METHYL)-3,4-DIHYDROXYTETRAHYDROFURAN-2- YL]PYRIDINIUM, ... (4 entities in total)
• 機能のキーワード: hydrolase, cd38, hydrolysis, nad, substrate specificity
• 由来する生物種: APLYSIA CALIFORNICA (CALIFORNIA SEA HARE)
• 細胞内の位置: Cytoplasmic vesicle: P29241
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 241244.51

構造登録者

Kotaka, M.,Graeff, R.,Zhang, L.H.,Lee, H.C.,Hao, Q. (登録日: 2011-08-02, 公開日: 2011-11-30, 最終更新日: 2024-10-16)

主引用文献

Kotaka, M.,Graeff, R.,Chen, Z.,Zhang, L.H.,Lee, H.C.,Hao, Q.
Structural Studies of Intermediates Along the Cyclization Pathway of Aplysia Adp-Ribosyl Cyclase.
J.Mol.Biol., 415:514-, 2012

PubMed Abstract: Cyclic ADP-ribose (cADPR) is a calcium messenger that can mobilize intracellular Ca²⁺ stores and activate Ca²⁺ influx to regulate a wide range of physiological processes. Aplysia cyclase is the first member of the ADP-ribosyl cyclases identified to catalyze the cyclization of NAD⁺ into cADPR. The catalysis involves a two-step reaction, the elimination of the nicotinamide ring and the cyclization of the intermediate resulting in the covalent attachment of the purine ring to the terminal ribose. Aplysia cyclase exhibits a high degree of leniency towards the purine base of its substrate, and the cyclization reaction takes place at either the N1- or the N7-position of the purine ring. To decipher the mechanism of cyclization in Aplysia cyclase, we used a crystallization setup with multiple Aplysia cyclase molecules present in the asymmetric unit. With the use of natural substrates and analogs, not only were we able to capture multiple snapshots during enzyme catalysis resulting in either N1 or N7 linkage of the purine ring to the terminal ribose, we were also able to observe, for the first time, the cyclized products of both N1 and N7 cyclization bound in the active site of Aplysia cyclase.

PubMed: 22138343
DOI: 10.1016/J.JMB.2011.11.022

実験手法

X-RAY DIFFRACTION (2 Å)