title: Structures of the cancer-related Aurora-A, FAK, and EphA2 protein kinases from nanovolume crystallography.
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.
authors.affiliation: Syrrx, Inc., 10410 Science Center Drive, San Diego, CA 92121, USA. jacek.nowakoski@syrrx.com
authors.forename: Jacek
authors.initials: J
authors.lastname: Nowakowski
authors.forename: Ciarán N
authors.initials: CN
authors.lastname: Cronin
authors.forename: Duncan E
authors.initials: DE
authors.lastname: McRee
authors.forename: Mark W
authors.initials: MW
authors.lastname: Knuth
authors.forename: Christian G
authors.initials: CG
authors.lastname: Nelson
authors.forename: Nikola P
authors.initials: NP
authors.lastname: Pavletich
authors.forename: Joe
authors.initials: J
authors.lastname: Rogers
authors.forename: Bi-Ching
authors.initials: BC
authors.lastname: Sang
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Scheibe
authors.forename: Ronald V
authors.initials: RV
authors.lastname: Swanson
authors.forename: Devon A
authors.initials: DA
authors.lastname: Thompson
mesh_terms: D000595:Amino Acid Sequence; D064127:Aurora Kinases; D018797:Cell Cycle Proteins; D018360:Crystallography, X-Ray; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D036103:Nanotechnology; D009369:Neoplasms / Q000201:enzymology*; D011487:Protein Conformation; D011494:Protein Kinases / Q000737:chemistry*; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases / Q000737:chemistry*; D036104:Receptor, EphA2 / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D029867:Xenopus Proteins
chemical_list: D018797:Cell Cycle Proteins; D029867:Xenopus Proteins; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D036104:Receptor, EphA2; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C112134:AURKA protein, Xenopus; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases