The R1275Q neuroblastoma mutant and certain ATP-competitive inhibitors stabilize alternative activation loop conformations of anaplastic lymphoma kinase

Abstract

Anaplastic lymphoma kinase (ALK) plays an important causative role in some cancers. Results: Novel views of the ALK activation loop are provided by several new crystal structures. Conclusion: Certain neuroblastoma mutations and inhibitors stabilize alternative, inactive ALK conformations. Significance: Novel kinase conformations may aid the design of a new generation of selective ALK inhibitors. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.