2JVN

Domain C of human PARP-1

2JVN の概要

• エントリーDOI: 10.2210/pdb2jvn/pdb
• 分子名称: Poly [ADP-ribose] polymerase 1, ZINC ION (2 entities in total)
• 機能のキーワード: protein, parp, adp-ribosylation, dna damage, dna repair, dna-binding, glycosyltransferase, metal-binding, nad, nucleus, phosphorylation, transferase, zinc-finger
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: P09874
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14562.32

構造登録者

Hoffman, D.,Tao, Z.,Liu, H. (登録日: 2007-09-24, 公開日: 2008-05-13, 最終更新日: 2024-05-01)

主引用文献

Tao, Z.,Gao, P.,Hoffman, D.W.,Liu, H.W.
Domain C of human poly(ADP-ribose) polymerase-1 is important for enzyme activity and contains a novel zinc-ribbon motif.
Biochemistry, 47:5804-5813, 2008

PubMed Abstract: Poly(ADP-ribose) polymerase-1 (PARP-1) is a multimodular nuclear protein that participates in many fundamental cellular activities. Stimulated by binding to nicked DNA, PARP-1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins using NAD (+) as a substrate. In this work, NMR methods were used to determine the solution structure of human PARP-1 protein. Domain C was found to contain a zinc-binding motif of three antiparallel beta-strands with four conserved cysteines positioned to coordinate the metal ligand, in addition to a helical region. The zinc-binding motif is structurally reminiscent of the "zinc-ribbon" fold, but with a novel spacing between the conserved cysteines (CX2CX12CX 9C). Domain C alone does not appear to bind to DNA. Interestingly, domain C is essential for PARP-1 activity, since a mixture containing nicked DNA and the PARP-1 ABDEF domains has only basal enzymatic activity, while the addition of domain C to the mixture initiated NAD (+) hydrolysis and the formation of poly(ADP-ribose), as detected by an NMR-based assay and autoradiography. The structural model for domain C in solution provides an important framework for further studies aimed at improving our understanding of how the various domains within the complex PARP-1 enzyme play their respective roles in regulating the enzyme activity when cells are under conditions of genotoxic stress.

PubMed: 18452307
DOI: 10.1021/bi800018a

実験手法

SOLUTION NMR