Human Family With Sequence Similarity 83 Member B (FAM83B); A Target Enabling Package
Creators
- Daniel M. Pinkas1
- Joshua C. Bufton1
- Alice E. Fox1
- Gian Filippo Ruda1
- Romain Talon1
- Tobias Krojer1
- Anthony R. Bradley1
- Frank von Delft1
- Paul E. Brennan1
- Luke J. Fulcher2
- Polyxeni Bozatzi2
- Theresa Tachi-Menson2
- Kevin Z. L. Wu2
- Timothy D. Cummins2
- Karen Dunbar2
- Sabin Shrestha2
- Nicola T. Wood2
- Simone Weidlich2
- Thomas J. Macartney2
- Joby Varghese2
- Robert Gourlay2
- David G. Campbell2
- Luke D. Hutchinson2
- Janis Vogt2
- Fay Cooper2
- Kevin S. Dingwell3
- James C. Smith3
- Gopal P. Sapkota3
- Alex N. Bullock1
- 1. Structural Genomics Consortium
- 2. MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee
- 3. The Francis Crick Institure, London
Description
FAM83A-H are newly identified oncogenes characterised by a conserved DUF1669 domain. FAM83B can substitute for RAS to promote malignant transformation. Ablation of FAM83B or mutation of Lys230 inhibits malignant phenotypes, implicating FAM83B as potential therapeutic target. As part of this TEP, we solved the first crystal structures from the FAM83 family, including FAM83A and FAM83B. The structures of the DUF1669 domain reveal a phospholipase D-like fold lacking conservation of key catalytic residues. We deorphanise the FAM83 DUF1669 domain as a critical docking scaffold for binding of casein kinase 1 isoforms. Finally, using XChem fragment screening we report chemical fragments that bind to Lys230 in the central pocket of the DUF1669 and form starting points for potential drug development.
Notes
Files
FAM83_TEP.pdf
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Additional details
Related works
- Is part of
- https://www.thesgc.org/tep (URL)
Funding
- A UK Hub to Catalyse Open Target Discovery. 106169
- Wellcome Trust