7POX

TNKS2 in complex with OM-1700, treated with H2O2

これはPDB形式変換不可エントリーです。

7POX の概要

• エントリーDOI: 10.2210/pdb7pox/pdb
• 分子名称: Poly [ADP-ribose] polymerase tankyrase-2, N-[3-[5-(5-ethoxypyridin-2-yl)-4-(2-fluorophenyl)-1,2,4-triazol-3-yl]cyclobutyl]pyridine-2-carboxamide (3 entities in total)
• 機能のキーワード: zinc, coordination, enzyme, poly-adp-ribosylation, inhibitor, h2o2, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 50573.16

構造登録者

Sowa, S.T.,Lehtio, L. (登録日: 2021-09-10, 公開日: 2022-05-04, 最終更新日: 2024-01-31)

主引用文献

Sowa, S.T.,Lehtio, L.
The zinc-binding motif in tankyrases is required for the structural integrity of the catalytic ADP-ribosyltransferase domain.
Open Biology, 12:210365-210365, 2022

PubMed Abstract: Tankyrases are ADP-ribosylating enzymes that regulate many physiological processes in the cell and are considered promising drug targets for cancer and fibrotic diseases. The catalytic ADP-ribosyltransferase domain of tankyrases contains a unique zinc-binding motif of unknown function. Recently, this motif was suggested to be involved in the catalytic activity of tankyrases. In this work, we set out to study the effect of the zinc-binding motif on the activity, stability and structure of human tankyrases. We generated mutants of human tankyrase (TNKS) 1 and TNKS2, abolishing the zinc-binding capabilities, and characterized the proteins biochemically and biophysically . We further generated a crystal structure of TNKS2, in which the zinc ion was oxidatively removed. Our work shows that the zinc-binding motif in tankyrases is a crucial structural element which is particularly important for the structural integrity of the acceptor site. While mutation of the motif rendered TNKS1 inactive, probably due to introduction of major structural defects, the TNKS2 mutant remained active and displayed an altered activity profile compared to the wild-type.

PubMed: 35317661
DOI: 10.1098/rsob.210365

実験手法

X-RAY DIFFRACTION (2.5 Å)