The zinc-binding motif in tankyrases is required for the structural integrity and proper function of the catalytic domain
Sowa, S. T.; Lehtiö, L.
Show abstract
Tankyrases are ADP-ribosylating enzymes that regulate many physiological processes in the cell and they are therefore possible drug targets for cancer and fibrotic diseases. The catalytic ADP-ribosyl-transferase domain of tankyrases contains a unique zinc-binding motif of unknown function. Recently, this motif was suggested to be involved in the catalytic activity of tankyrases. In this work, we set out to study the effect of the zinc-binding motif on activity, stability and structure of human tankyrases. We generated mutants of human TNKS1 and TNKS2 abolishing the zinc-binding capabilities and characterized the proteins biochemically and biophysically in vitro. We further generated a crystal structure of TNKS2, in which the zinc ion was oxidatively removed. Our work shows that the zinc-binding motif in tankyrases is a crucial structural element which is particularly important for the structural integrity of the acceptor site. While mutation of the motif rendered TNKS1 inactive likely due to introduction of major structural defects, the TNKS2 mutant remained active and displayed a different activity profile compared to the wild type.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Understanding ATP binding to DosS catalytic domain with a short ATP-lid 94%
- Structural characterization of functionally important chloride binding sites in the marine Vibrio alkaline phosphatase 94%
- Kinetic Characterization and Computational Modeling of the Escherichia coli Heptosyltransferase II: Exploring the Role of Protein Dynamics in Catalysis for a GT-B Glycosyltransferase 94%
Similar papers in this journal
- Phenol Sensing in Nature Modulated via a Conformational Switch Governed by Dynamic Allostery 95%
- Evolution of an interaction between disordered proteins resulted in increased heterogeneity of the binding transition state 94%
- Thermostable designed ankyrin repeat proteins (DARPins) as building blocks for innovative drugs 94%
Similar papers in this journal
- The WRC domain of GRF transcription factors. Structure and DNA recognition 93%
- Systematic enhancement of protein crystallization efficiency by bulk lysine-to-arginine (KR) substitution 93%
- Structural and biochemical analyses of selectivity determinants in chimeric Streptococcus Class A sortase enzymes 93%
Similar papers in this journal
- Insights into the conformational dynamics of the cytoplasmic domain of metal-sensing sensor histidine kinase ZraS 95%
- Interfacial residues in protein-protein complexes are in the eyes of the beholder 94%
- Crystal structure of FAD-independent methylene-tetrahydrofolate reductase from Mycobacterium hassiacum 94%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.