2jvn

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Template:STRUCTURE 2jvn

Domain C of human PARP-1

Overview

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 (C X 2C X 12C X 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.

About this Structure

2JVN is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Domain C of Human Poly(ADP-ribose) Polymerase-1 Is Important for Enzyme Activity and Contains a Novel Zinc-Ribbon Motif(,)., Tao Z, Gao P, Hoffman DW, Liu HW, Biochemistry. 2008 May 2;. PMID:18452307 Page seeded by OCA on Wed May 14 11:19:58 2008