PMID- 27480927 OWN - NLM STAT- MEDLINE DCOM- 20170529 LR - 20171127 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 478 IP - 2 DP - 2016 Sep 16 TI - Crystal structure of the kinase domain of human protein tyrosine kinase 6 (PTK6) at 2.33 A resolution. PG - 637-42 LID - S0006-291X(16)31243-8 [pii] LID - 10.1016/j.bbrc.2016.07.121 [doi] AB - 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 A 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 approximately 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 alphaC-helix-out conformation. CI - Copyright (c) 2016 Elsevier Inc. All rights reserved. FAU - Thakur, Manish Kumar AU - Thakur MK AD - Department of Biochemistry, University of Mysore, Mysore, 570005, India; Department of Structural Biology, Jubilant Biosys Ltd, Bangalore, 560022, India. FAU - Kumar, Amit AU - Kumar A AD - Department of Structural Biology, Jubilant Biosys Ltd, Bangalore, 560022, India. FAU - Birudukota, Swarnakumari AU - Birudukota S AD - Department of Structural Biology, Jubilant Biosys Ltd, Bangalore, 560022, India. FAU - Swaminathan, Srinivasan AU - Swaminathan S AD - Department of Structural Biology, Jubilant Biosys Ltd, Bangalore, 560022, India. FAU - Tyagi, Rajiv AU - Tyagi R AD - Department of Structural Biology, Jubilant Biosys Ltd, Bangalore, 560022, India. FAU - Gosu, Ramachandraiah AU - Gosu R AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160730 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Neoplasm Proteins) RN - 0 (Recombinant Proteins) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.2 (PTK6 protein, human) SB - IM MH - Amino Acid Sequence MH - Animals MH - Baculoviridae/genetics/metabolism MH - Cloning, Molecular MH - Crystallography, X-Ray MH - Enzyme Assays MH - Gene Expression MH - Humans MH - Kinetics MH - Models, Molecular MH - *Mutation MH - Neoplasm Proteins/*chemistry/genetics/metabolism MH - Protein Conformation, alpha-Helical MH - Protein Domains MH - Protein-Tyrosine Kinases/*chemistry/genetics/metabolism MH - Recombinant Proteins/chemistry/genetics/metabolism MH - Sequence Alignment MH - Sf9 Cells MH - Spodoptera MH - Structure-Activity Relationship OTO - NOTNLM OT - BRK OT - Cancer OT - Kinase domain OT - Non-receptor tyrosine kinase OT - PTK6 OT - X-ray crystal structure EDAT- 2016/08/03 06:00 MHDA- 2017/05/30 06:00 CRDT- 2016/08/03 06:00 PHST- 2016/07/20 00:00 [received] PHST- 2016/07/28 00:00 [accepted] PHST- 2016/08/03 06:00 [entrez] PHST- 2016/08/03 06:00 [pubmed] PHST- 2017/05/30 06:00 [medline] AID - S0006-291X(16)31243-8 [pii] AID - 10.1016/j.bbrc.2016.07.121 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2016 Sep 16;478(2):637-42. doi: 10.1016/j.bbrc.2016.07.121. Epub 2016 Jul 30.