| 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 Å 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. |
| Keywords: |
controlled study; unclassified drug; molecular genetics; protein conformation; protein domain; neoplasm; neoplasms; cell cycle protein; cell cycle proteins; protein kinases; protein; enzymology; protein serine threonine kinase; protein tyrosine kinase; chemistry; enzyme regulation; amino acid sequence; molecular sequence data; sequence homology, amino acid; protein-serine-threonine kinases; nucleotide sequence; carcinoma; crystal structure; models, molecular; crystallography, x-ray; chemical structure; protein-tyrosine kinases; ephrin receptor a2; sequence homology; protein family; x ray crystallography; enzyme structure; protein kinase; focal adhesion kinase; phosphotransferase inhibitor; nanotechnology; aurora a kinase; focal adhesion protein-tyrosine kinases; crystallography; focal adhesion kinase 1; ptk2 protein, human; receptor, epha2; xenopus proteins; fak; ephrin receptor; diffraction; crystal; aurora kinase; epha2; cancer; humans; human; priority journal; article; aurora; nanovolume crystallography; eg2 protein, xenopus; xenopus protein
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