title: Crystal structure of the kinase domain of human protein tyrosine kinase 6 (PTK6) at 2.33 Å resolution.
abstract: Human Protein tyrosine kinase 6 (PTK6) (EC:2.7.10.2), also known as the breast tumor kinase (BRK), is an intracellular non-receptor Src-related tyrosine kinase expressed in a majority of human breast tumors and breast cancer cell lines, but its expression is low or completely absent in normal mammary glands. In the recent past, several studies have suggested that PTK6 is a potential therapeutic target in cancer. To understand its structural and functional properties, the PTK6 kinase domain (PTK6-KD) gene was cloned, overexpressed in a baculo-insect cell system, purified and crystallized at room temperature. X-ray diffraction data to 2.33 Å resolution was collected on a single PTK6-KD crystal, which belonged to the triclinic space group P1. The Matthews coefficient calculation suggested the presence of four protein molecules per asymmetric unit, with a solvent content of ∼50%.The structure has been solved by molecular replacement and crystal structure data submitted to the protein data bank under the accession number 5D7V. This is the first report of apo PTK6-KD structure crystallized in DFG-in and αC-helix-out conformation.
authors.affiliation: Department of Biochemistry, University of Mysore, Mysore, 570005, India; Department of Structural Biology, Jubilant Biosys Ltd, Bangalore, 560022, India.
authors.forename: Manish Kumar
authors.initials: MK
authors.lastname: Thakur
authors.affiliation: Department of Structural Biology, Jubilant Biosys Ltd, Bangalore, 560022, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Structural Biology, Jubilant Biosys Ltd, Bangalore, 560022, India.
authors.forename: Swarnakumari
authors.initials: S
authors.lastname: Birudukota
authors.affiliation: Department of Structural Biology, Jubilant Biosys Ltd, Bangalore, 560022, India.
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Swaminathan
authors.affiliation: Department of Structural Biology, Jubilant Biosys Ltd, Bangalore, 560022, India.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Tyagi
authors.affiliation: Department of Biochemistry, University of Mysore, Mysore, 570005, India; Department of Structural Biology, Jubilant Biosys Ltd, Bangalore, 560022, India. Electronic address: ramachandraiah_gosu@jubilantbiosys.com.
authors.forename: Ramachandraiah
authors.initials: R
authors.lastname: Gosu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016367:Baculoviridae / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D057075:Enzyme Assays; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D009154:Mutation; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000072756:Protein Conformation, alpha-Helical; D000072417:Protein Domains; D011505:Protein-Tyrosine Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D061987:Sf9 Cells; D018411:Spodoptera; D013329:Structure-Activity Relationship
chemical_list: D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D011505:Protein-Tyrosine Kinases; C088375:PTK6 protein, human
keywords: BRK; Cancer; Kinase domain; Non-receptor tyrosine kinase; PTK6; X-ray crystal structure