2RF5

Crystal structure of human tankyrase 1- catalytic PARP domain

Summary for 2RF5

• Entry DOI: 10.2210/pdb2rf5/pdb
• Descriptor: Tankyrase-1, ZINC ION, GLYCEROL, ... (4 entities in total)
• Functional Keywords: catalytic fragment, parp, structural genomics, structural genomics consortium, sgc, adp-ribosylation, ank repeat, chromosomal protein, glycosyltransferase, golgi apparatus, membrane, mrna transport, nad, nuclear pore complex, nucleus, phosphorylation, protein transport, telomere, transferase, translocation, transport
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: O95271
• Total number of polymer chains: 1
• Total formula weight: 29574.58

Authors

Lehtio, L.,Karlberg, T.,Arrowsmith, C.H.,Berglund, H.,Busam, R.,Collins, R.,Dahlgren, L.G.,Edwards, A.M.,Flodin, S.,Flores, A.,Graslund, S.,Hammarstrom, M.,Herman, M.D.,Holmberg-Schiavone, L.,Johansson, I.,Kallas, A.,Kotenyova, T.,Moche, M.,Nordlund, P.,Nyman, T.,Persson, C.,Sagemark, J.,Sundstrom, M.,Thorsell, A.G.,Tresaugues, L.,van den Berg, S.,Welin, M.,Weigelt, J.,Structural Genomics Consortium (SGC) (deposition date: 2007-09-28, release date: 2007-10-09, Last modification date: 2023-08-30)

Primary citation

Lehtio, L.,Collins, R.,van den Berg, S.,Johansson, A.,Dahlgren, L.G.,Hammarstrom, M.,Helleday, T.,Holmberg-Schiavone, L.,Karlberg, T.,Weigelt, J.
Zinc binding catalytic domain of human tankyrase 1.
J.Mol.Biol., 379:136-145, 2008

PubMed Abstract: 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.

PubMed: 18436240
DOI: 10.1016/j.jmb.2008.03.058

Experimental method

X-RAY DIFFRACTION (2.3 Å)