9BPY

Human PARP1 ART domain bound to NAD+ analogs benzamide adenine dinucleotide and carba-NAD+

9BPY の概要

• エントリーDOI: 10.2210/pdb9bpy/pdb
• 分子名称: Poly [ADP-ribose] polymerase 1, [(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl [(2R,3S,4R,5S)-5-(3-carbamoylphenyl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl dihydrogen diphosphate (non-preferred name), CARBA-NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (4 entities in total)
• 機能のキーワード: parp1, nad+ analog, adp-ribosyl transferase, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 123325.31

構造登録者

Langelier, M.F.,Pascal, J.M. (登録日: 2024-05-08, 公開日: 2025-02-05)

主引用文献

Langelier, M.F.,Mirhasan, M.,Gilbert, K.,Sverzhinksy, A.,Furtos, A.,Pascal, J.M.
PARP enzyme de novo synthesis of protein-free poly(ADP-ribose).
Mol.Cell, 84:4758-4773.e6, 2024

PubMed Abstract: PARP enzymes transfer ADP-ribose from NAD onto proteins as a covalent modification that regulates multiple aspects of cell biology. Here, we identify an undiscovered catalytic activity for human PARP1: de novo generation of free PAR molecules that are not attached to proteins. Free PAR production arises when a molecule of NAD or ADP-ribose docks in the PARP1 acceptor site and attaches to an NAD molecule bound to the donor site, releasing nicotinamide and initiating ADP-ribose chains that emanate from NAD/ADP-ribose rather than protein. Free PAR is also produced by human PARP2 and the PARP enzyme Tankyrase. We demonstrate that free PAR in cells is generated mostly by PARP1 de novo synthesis activity rather than by PAR-degrading enzymes PAR glycohydrolase (PARG), ARH3, and TARG1 releasing PAR from protein. The coincident production of free PAR and protein-linked modifications alters models for PAR signaling and broadens the scope of PARP enzyme signaling capacity.

PubMed: 39536748
DOI: 10.1016/j.molcel.2024.10.024

実験手法

X-RAY DIFFRACTION (2.8 Å)