2rf5

File:2rf5.jpg

Crystal structure of human tankyrase 1- catalytic PARP domain

OverviewOverview

Tankyrases are recently discovered proteins implicated in many important functions in the cell including telomere homeostasis and mitosis. Tankyrase modulates the activity of target proteins through poly(ADP-ribosyl)ation, and here we report the structure of the catalytic poly(ADP-ribose) polymerase (PARP) domain of human tankyrase 1. This is the first structure of a PARP domain from the tankyrase subfamily. The present structure reveals that tankyrases contain a short zinc-binding motif, which has not been predicted. Tankyrase activity contributes to telomere elongation observed in various cancer cells and tankyrase inhibition has been suggested as a potential route for cancer therapy. In comparison with other PARPs, significant structural differences are observed in the regions lining the substrate-binding site of tankyrase 1. These findings will be of great value to facilitate structure-based design of selective PARP inhibitors, in general, and tankyrase inhibitors, in particular.

About this StructureAbout this Structure

2RF5 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Zinc binding catalytic domain of human tankyrase 1., Lehtio L, Collins R, van den Berg S, Johansson A, Dahlgren LG, Hammarstrom M, Helleday T, Holmberg-Schiavone L, Karlberg T, Weigelt J, J Mol Biol. 2008 May 23;379(1):136-45. Epub 2008 Apr 3. PMID:18436240 Page seeded by OCA on Wed Jun 4 09:59:12 2008