Zinc binding catalytic domain of human tankyrase 1

被引：58

作者：

Lehtioe, Lari ^{[1
]}

Collins, Ruairi ^{[1
]}

van den Berg, Susanne ^{[1
]}

Johansson, Andreas ^{[1
]}

Dahlgren, Lars-Goeran ^{[1
]}

Hammarstroem, Martin ^{[1
]}

Helleday, Thomas ^{[2
,3
]}

Holmberg-Schiavone, Lovisa ^{[1
]}

Karlberg, Tobias ^{[1
]}

Weigelt, Johan ^{[1
]}

机构：

[1] Karolinska Inst, Struct Genom Consortium, Dept Med Biochem & Biophys, S-17177 Stockholm, Sweden

[2] Univ Stockholm, Dept Genet Microbiol & Toxicol, S-10691 Stockholm, Sweden

[3] Univ Oxford, Oxford OX3 7LJ, England

来源：

JOURNAL OF MOLECULAR BIOLOGY | 2008年 / 379卷 / 01期

基金：

英国医学研究理事会;

关键词：

tankyrase; poly(ADP-ribose) polymerase; inhibitor design; zinc;

D O I：

10.1016/j.jmb.2008.03.058

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：136 / 145

页数：10

共 61 条

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