Download MendeleyCrystal Structures of Ask1-Inhibtor Complexes Provide a Platform for Structure Based Drug Design.
Singh, O., Shillings, A., Craggs, P., Wall, I., Rowland, P., Skarzynski, T., Hobbs, C.I., Hardwick, P., Tanner, R., Blunt, M., Witty, D.R., Smith, K.J.(2013) Protein Sci 22: 1071
- PubMed: 23776076
- DOI: https://doi.org/10.1002/pro.2298
- Primary Citation of Related Structures:
4BF2, 4BHN, 4BIB, 4BIC, 4BID, 4BIE - PubMed Abstract:
ASK1, a member of the MAPK Kinase Kinase family of proteins has been shown to play a key role in cancer, neurodegeneration and cardiovascular diseases and is emerging as a possible drug target. Here we describe a 'replacement-soaking' method that has enabled the high-throughput X-ray structure determination of ASK1/ligand complexes. Comparison of the X-ray structures of five ASK1/ligand complexes from 3 different chemotypes illustrates that the ASK1 ATP binding site is able to accommodate a range of chemical diversity and different binding modes. The replacement-soaking system is also able to tolerate some protein flexibility. This crystal system provides a robust platform for ASK1/ligand structure determination and future structure based drug design.
Organizational Affiliation:
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, United Kingdom.
