title: The structure of human tau-tubulin kinase 1 both in the apo form and in complex with an inhibitor.
abstract: Tau-tubulin kinase 1 (TTBK1) is a dual-specificity (serine/threonine and tyrosine) kinase belonging to the casein kinase 1 superfamily. TTBK1 is a neuron-specific kinase that regulates tau phosphorylation. Hyperphosphorylation of tau is implicated in the pathogenesis of Alzheimer's disease. Two kinase-domain constructs of TTBK1 were expressed in a baculovirus-infected insect-cell system and purified. The purified TTBK1 kinase-domain proteins were crystallized using the hanging-drop vapor-diffusion method. X-ray diffraction data were collected and the structure of TTBK1 was determined by molecular replacement both as an apo structure and in complex with a kinase inhibitor.
authors.affiliation: Molecular Discovery Technologies, Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Kiefer
authors.affiliation: Molecular Discovery Technologies, Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA.
authors.forename: Chiehying J
authors.initials: CJ
authors.lastname: Chang
authors.affiliation: Molecular Discovery Technologies, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: S Roy
authors.initials: SR
authors.lastname: Kimura
authors.affiliation: Molecular Discovery Technologies, Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA.
authors.forename: Mian
authors.initials: M
authors.lastname: Gao
authors.affiliation: Molecular Discovery Technologies, Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA.
authors.forename: Dianlin
authors.initials: D
authors.lastname: Xie
authors.affiliation: Molecular Discovery Technologies, Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA.
authors.forename: Yaqun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Guifen
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Neuroscience Biology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Martin B
authors.initials: MB
authors.lastname: Gill
authors.affiliation: Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Harold
authors.initials: H
authors.lastname: Mastalerz
authors.affiliation: Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Lorin A
authors.initials: LA
authors.lastname: Thompson
authors.affiliation: Neuroscience Biology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Cacace
authors.affiliation: Molecular Discovery Technologies, Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Sheriff
mesh_terms: D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D003460:Crystallization; D018360:Crystallography, X-Ray; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000737:chemistry*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry*; D061987:Sf9 Cells; D013379:Substrate Specificity
chemical_list: D047428:Protein Kinase Inhibitors; C095903:tau-tubulin kinase; D017346:Protein Serine-Threonine Kinases
keywords: TTBK1; inhibitors; kinase domain