2riq

File:2riq.jpg

spinqualitylabelsall models 2riq, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal Structure of the Third Zinc-binding domain of human PARP-1

OverviewOverview

PARP-1 is a chromatin-associated enzyme with multiple cellular functions, including DNA repair, transcriptional regulation, and cell signaling., PARP-1 has a modular architecture with six independent domains comprising, the 113 kDa polypeptide. Two zinc-finger domains at the N-terminus of, PARP-1 bind to DNA and thereby activate the catalytic domain situated at, the C-terminus of the enzyme. The tight coupling of DNA binding and, catalytic activities is critical to the cellular regulation of PARP-1, function, however, the mechanism for coordinating these activities remains, an unsolved problem. Here, we demonstrate using spectroscopic and, crystallographic analysis that human PARP-1 has a third zinc-binding, domain. Biochemical mutagenesis and deletion analysis indicate that this, region mediates inter-domain contacts important for DNA-dependent enzyme, activation. The crystal structure of the third zinc-binding domain reveals, a zinc ribbon fold and suggests conserved residues that could form, inter-domain contacts. The new zinc-binding domain self-associates in the, crystal lattice to form a homodimer with a head-to-tail arrangement. The, structure of the homodimer provides a scaffold for assembling the, activated state of PARP-1 and suggests a mechanism for coupling the DNA, binding and catalytic functions of PARP-1.

About this StructureAbout this Structure

2RIQ is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as NAD(+) ADP-ribosyltransferase, with EC number 2.4.2.30 Full crystallographic information is available from OCA.

ReferenceReference

A third zinc-binding domain of human PARP-1 coordinates DNA-dependent enzyme activation., Langelier MF, Servent KM, Rogers EE, Pascal JM, J Biol Chem. 2007 Nov 30;. PMID:18055453

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