Development and structural analysis of adenosine site binding tankyrase inhibitors.
Oulu, Finland. In Bioorg Med Chem Lett, Feb 2016
The scaffold also enables a fine modulation of selectivity towards either tankyrase 1 or tankyrase 2. In order to get insight about the binding mode of the inhibitors, we solved crystal structures of the compounds in complex with tankyrase 2. The compounds bind to the adenosine pocket of the catalytic domain and cause changes in the protein structure that are modulated by the chemical modifications of the compounds.
Tankyrases as drug targets.
Oulu, Finland. In Febs J, 2013
Tankyrase 1 and tankyrase 2 are poly(ADP-ribosyl)ases that are distinguishable from other members of the enzyme family by the structural features of the catalytic domain, and the presence of a sterile α-motif multimerization domain and an ankyrin repeat protein-interaction domain.
Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling.
Cambridge, United States. In Nature, 2009
Using a quantitative chemical proteomic approach, we discovered that XAV939 stabilizes axin by inhibiting the poly-ADP-ribosylating enzymes tankyrase 1 and tankyrase 2. Both tankyrase isoforms interact with a highly conserved domain of axin and stimulate its degradation through the ubiquitin-proteasome pathway.
Tankyrase function at telomeres, spindle poles, and beyond.
New York City, United States. In Biochimie, 2008
An understanding of how tankyrase 1 functions at telomeres has been confounded by its complexity; it localizes to multiple subcellular sites, it has many diverse binding partners, and it has a closely related homolog (tankyrase 2) with which it may functionally overlap.
The emerging role of poly(ADP-ribose) polymerase-1 in longevity.
Konstanz, Germany. In Int J Biochem Cell Biol, 2005
In particular, tankyrase-1, tankyrase-2, PARP-2 as well as PARP-1 have been found in association with telomeric DNA and are able to poly(ADP-ribosyl)ate the telomere-binding proteins TRF-1 and TRF-2, thus blocking their DNA-binding activity and controlling telomere extension by telomerase.