4BIB

Crystal Structures of Ask1-inhibitor Complexes

Summary for 4BIB

• Entry DOI: 10.2210/pdb4bib/pdb
• Related: 4BF2 4BHN 4BIC 4BID 4BIE
• Descriptor: MITOGEN-ACTIVATED PROTEIN KINASE KINASE KINASE 5, 3-cyano-4-(piperidin-4-yloxy)-1H-indole-7-carboxamide, GLYCEROL, ... (5 entities in total)
• Functional Keywords: transferase
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm: Q99683
• Total number of polymer chains: 2
• Total formula weight: 72006.74

Authors

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. (deposition date: 2013-04-10, release date: 2013-07-03, Last modification date: 2023-12-20)

Primary citation

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.
Crystal Structures of Ask1-Inhibtor Complexes Provide a Platform for Structure Based Drug Design.
Protein Sci., 22:1071-, 2013

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.

PubMed: 23776076
DOI: 10.1002/PRO.2298

Experimental method

X-RAY DIFFRACTION (2.43 Å)