Structures of the cancer-related Aurora-A, FAK, and EphA2 protein kinases from nanovolume crystallography

Structure. 2002 Dec;10(12):1659-67. doi: 10.1016/s0969-2126(02)00907-3.

Abstract

Protein kinases are important drug targets in human cancers, inflammation, and metabolic diseases. This report presents the structures of kinase domains for three cancer-associated protein kinases: ephrin receptor A2 (EphA2), focal adhesion kinase (FAK), and Aurora-A. The expression profiles of EphA2, FAK, and Aurora-A in carcinomas suggest that inhibitors of these kinases may have inherent potential as therapeutic agents. The structures were determined from crystals grown in nanovolume droplets, which produced high-resolution diffraction data at 1.7, 1.9, and 2.3 A for FAK, Aurora-A, and EphA2, respectively. The FAK and Aurora-A structures are the first determined within two unique subfamilies of human kinases, and all three structures provide new insights into kinase regulation and the design of selective inhibitors.

MeSH terms

  • Amino Acid Sequence
  • Aurora Kinases
  • Cell Cycle Proteins
  • Crystallography, X-Ray
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Nanotechnology
  • Neoplasms / enzymology*
  • Protein Conformation
  • Protein Kinases / chemistry*
  • Protein-Serine-Threonine Kinases
  • Protein-Tyrosine Kinases / chemistry*
  • Receptor, EphA2 / chemistry*
  • Sequence Homology, Amino Acid
  • Xenopus Proteins

Substances

  • Cell Cycle Proteins
  • Xenopus Proteins
  • Protein Kinases
  • Protein-Tyrosine Kinases
  • Receptor, EphA2
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • PTK2 protein, human
  • AURKA protein, Xenopus
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases

Associated data

  • PDB/1MP8
  • PDB/1MQ4
  • PDB/1MQB