PDBsum entry 4bhn

Transferase

PDB id: 4bhn

Contents

Protein chain

256 a.a.

Ligands

BH9 ×2

GOL ×2

Waters ×216

References listed in PDB file

Key reference

• Title: Crystal structures of ask1-Inhibtor complexes provide a platform for structure-Based drug design.
• Authors: O.Singh, A.Shillings, P.Craggs, I.Wall, P.Rowland, T.Skarzynski, C.I.Hobbs, P.Hardwick, R.Tanner, M.Blunt, D.R.Witty, K.J.Smith.
• Ref.: Protein Sci, 2013, 22, 1071-1077. [DOI no: 10.1002/pro.2298]
• PubMed id: 23776076

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.