5ZJ5

Guanine-specific ADP-ribosyltransferase with NADH and GDP

5ZJ5 の概要

• エントリーDOI: 10.2210/pdb5zj5/pdb
• 分子名称: ADP-ribosyltransferase, 1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE, GUANOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: adp-ribosyltransferase, toxin, transferase
• 由来する生物種: Streptomyces coelicolor A3(2)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 38672.74

構造登録者

Yoshida, T.,Tsuge, H. (登録日: 2018-03-19, 公開日: 2018-08-08, 最終更新日: 2024-10-16)

主引用文献

Yoshida, T.,Tsuge, H.
Substrate N2atom recognition mechanism in pierisin family DNA-targeting, guanine-specific ADP-ribosyltransferase ScARP.
J. Biol. Chem., 293:13768-13774, 2018

PubMed Abstract: ScARP from the bacterium belongs to the pierisin family of DNA-targeting ADP-ribosyltransferases (ARTs). These enzymes ADP-ribosylate the N amino groups of guanine residues in DNA to yield N-(ADP-ribos-1-yl)-2'-deoxyguanosine. Although the structures of pierisin-1 and Scabin were revealed recently, the substrate recognition mechanisms remain poorly understood because of the lack of a substrate-binding structure. Here, we report the apo structure of ScARP and of ScARP bound to NADH and its GDP substrate at 1.50 and 1.57 Å resolutions, respectively. The bound structure revealed that the guanine of GDP is trapped between -ribose of NADH and Trp-159. Interestingly, N and N of guanine formed hydrogen bonds with the OE1 and NE2 atoms of Gln-162, respectively. We directly observed that the ADP-ribosylating toxin turn-turn (ARTT)-loop, including Trp-159 and Gln-162, plays a key role in the specificity of DNA-targeting, guanine-specific ARTs as well as protein-targeting ARTs such as the C3 exoenzyme. We propose that the ARTT-loop recognition is a common substrate-recognition mechanism in the pierisin family. Furthermore, this complex structure sheds light on similarities and differences among two subclasses that are distinguished by conserved structural motifs: H-Y-E in the ARTD subfamily and R-S-E in the ARTC subfamily. The spatial arrangements of the electrophile and nucleophile were the same, providing the first evidence for a common reaction mechanism in these ARTs. ARTC (including ScARP) uses the ARTT-loop for substrate recognition, whereas ARTD (represented by Arr) uses the C-terminal helix instead of the ARTT-loop. These observations could help inform efforts to improve ART inhibitors.

PubMed: 30072382
DOI: 10.1074/jbc.AC118.004412

実験手法

X-RAY DIFFRACTION (1.56811199264 Å)