1TOX

DIPHTHERIA TOXIN DIMER COMPLEXED WITH NAD

1TOX の概要

• エントリーDOI: 10.2210/pdb1tox/pdb
• 分子名称: DIPHTHERIA TOXIN (DIMERIC), NICOTINAMIDE-ADENINE-DINUCLEOTIDE (3 entities in total)
• 機能のキーワード: toxin, adp-ribosylation, glucosyltransferase, transferase, nad
• 由来する生物種: Corynephage beta
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 118149.57

構造登録者

Bell, C.E.,Eisenberg, D. (登録日: 1995-10-06, 公開日: 1996-06-10, 最終更新日: 2024-10-30)

主引用文献

Bell, C.E.,Eisenberg, D.
Crystal structure of diphtheria toxin bound to nicotinamide adenine dinucleotide.
Biochemistry, 35:1137-1149, 1996

PubMed Abstract: Diphtheria toxin (DT), a 58 kDa protein secreted by lysogenic strains of Corynebacterium diphtheriae, causes the disease diphtheria in humans by gaining entry into the cytoplasm of cells and inhibiting protein synthesis. Specifically, the catalytic (C) domain of DT transfers the ADP-ribose group of NAD to elongation factor-2 (EF-2), rendering EF-2 inactive. In order to investigate how the C-domain of DT binds NAD and catalyzes the ADP-ribosylation of EF-2, the crystal structure of DT in complex with NAD has been determined to 2.3 A resolution. This is the first crystal structure of an ADP-ribosyltransferase (ADP-RT) enzyme in complex with NAD and suggests the features of the ADP-RT fold which are important for NAD binding. The conformation of NAD in the complex and the proximity of the Glu148 carboxylate group of the C-domain to the scissile, N-glycosidic bond of NAD suggest plausible modes of catalysis of the ADP-ribosylation reaction. Residues 39-46 of the active-site loop of the C-domain become disordered upon NAD binding, suggesting a potential role for this loop in the recognition of the ADP-ribose acceptor substrate, EF-2. The negatively charged phosphates and two ribose hydroxyls of NAD are not in direct contact with any atoms of the C-domain. Instead, they form an exposed surface which appears to be presented for recognition by EF-2. Structural alignments of the DT-NAD complex with the structures of other members of the ADP-RT family suggest how NAD may bind to these other enzymes.

PubMed: 8573568
DOI: 10.1021/bi9520848

実験手法

X-RAY DIFFRACTION (2.3 Å)