2ADA

ATOMIC STRUCTURE OF ADENOSINE DEAMINASE COMPLEXED WITH A TRANSITION-STATE ANALOG: UNDERSTANDING CATALYSIS AND IMMUNODEFICIENCY MUTATIONS

「1ADA」から置き換えられました

2ADA の概要

• エントリーDOI: 10.2210/pdb2ada/pdb
• 分子名称: ADENOSINE DEAMINASE, ZINC ION, 6-HYDROXY-7,8-DIHYDRO PURINE NUCLEOSIDE, ... (4 entities in total)
• 機能のキーワード: hydrolase, amino, zinc cofactor, beta/alpha barrel, transition-state inhibitor
• 由来する生物種: Mus musculus (house mouse)
• 細胞内の位置: Cell membrane; Peripheral membrane protein; Extracellular side (By similarity): P03958
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 40381.24

構造登録者

Wilson, D.K.,Quiocho, F.A. (登録日: 1994-12-02, 公開日: 1995-03-31, 最終更新日: 2024-02-14)

主引用文献

Wilson, D.K.,Rudolph, F.B.,Quiocho, F.A.
Atomic structure of adenosine deaminase complexed with a transition-state analog: understanding catalysis and immunodeficiency mutations.
Science, 252:1278-1284, 1991

PubMed Abstract: The crystal structure of a murine adenosine deaminase complexed with 6-hydroxyl-1,6-dihydropurine ribonucleoside, a nearly ideal transition-state analog, has been determined and refined at 2.4 angstrom resolution. The structure is folded as an eight-stranded parallel alpha/beta barrel with a deep pocket at the beta-barrel COOH-terminal end wherein the inhibitor and a zinc are bound and completely sequestered. The presence of the zinc cofactor and the precise structure of the bound analog were not previously known. The 6R isomer of the analog is very tightly held in place by the coordination of the 6-hydroxyl to the zinc and the formation of nine hydrogen bonds. On the basis of the structure of the complex a stereoselective addition-elimination or SN2 mechanism of the enzyme is proposed with the zinc atom and the Glu and Asp residues playing key roles. A molecular explanation of a hereditary disease caused by several point mutations of an enzyme is also presented.

PubMed: 1925539

実験手法

X-RAY DIFFRACTION (2.4 Å)