Professor Peter Colman
Details
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Division: Structural Biology
Research Overview
The intrinsic pathway to cell death is controlled by the Bcl-2 family of proteins. High levels of these proteins can render cells resistant to chemotoxic insults. Such resistance is a hallmark of certain cancers. Some viruses express proteins which block the intrinsic cell death pathway by functioning as mimics of Bcl-2. Understanding the interactions of the Bcl-2 family proteins with their natural antagonists may inform the discovery of organic ligands capable of killing cells.
Research Interests
- Structure and function of the Bcl-2 protein family
- The structure and function of viral Bcl-2 homologues
Selected Publications
- Lee EF, Sadowsky JD, Smith BJ, Czabotar PE, Peterson-Kaufman KJ, Colman PM, Gellman SH, Fairlie WD. High-Resolution Structural Characterization of a Helical alpha/beta-Peptide Foldamer Bound to the Anti-Apoptotic Protein Bcl-x(L). Angew Chem Int Ed Engl. 2009 Feb 19; PMID: 19229915 [PubMed - as supplied by publisher]
- Lessene G, Czabotar PE, Colman PM. BCL-2 family antagonists for cancer therapy. Nat Rev Drug Discov. 2008 Dec;7(12):989-1000 PMID: 19043450 [PubMed - indexed for MEDLINE]
- Lee EF, Chen L, Yang H, Colman PM, Huang DC, Fairlie WD. EGL-1 BH3 mutants reveal the importance of protein levels and target affinity for cell-killing potency. Cell Death Differ. 2008 Oct;15(10):1609-18 PMID: 18566606 [PubMed - indexed for MEDLINE]
- Kvansakul M, Yang H, Fairlie WD, Czabotar PE, Fischer SF, Perugini MA, Huang DC, Colman PM. Vaccinia virus anti-apoptotic F1L is a novel Bcl-2-like domain-swapped dimer that binds a highly selective subset of BH3-containing death ligands. Cell Death Differ. 2008 Oct;15(10):1564-71 PMID: 18551131 [PubMed - indexed for MEDLINE]
- Dewson G, Kratina T, Sim HW, Puthalakath H, Adams JM, Colman PM, Kluck RM. To trigger apoptosis, Bak exposes its BH3 domain and homodimerizes via BH3:groove interactions. Mol Cell. 2008 May 9;30(3):369-80 PMID: 18471982 [PubMed - indexed for MEDLINE]
- Lee EF, Czabotar PE, van Delft MF, Michalak EM, Boyle MJ, Willis SN, Puthalakath H, Bouillet P, Colman PM, Huang DC, Fairlie WD. A novel BH3 ligand that selectively targets Mcl-1 reveals that apoptosis can proceed without Mcl-1 degradation. J Cell Biol. 2008 Jan 28;180(2):341-55 PMID: 18209102 [PubMed - indexed for MEDLINE]
- Lee EF, Czabotar PE, Smith BJ, Deshayes K, Zobel K, Colman PM, Fairlie WD. Crystal structure of ABT-737 complexed with Bcl-xL: implications for selectivity of antagonists of the Bcl-2 family.
Cell Death Differ. 2007 Sep;14(9):1711-3 PMID: 17572662 [PubMed - indexed for MEDLINE] - Czabotar PE, Lee EF, van Delft MF, Day CL, Smith BJ, Huang DC, Fairlie WD, Hinds MG, Colman PM. Structural insights into the degradation of Mcl-1 induced by BH3 domains. Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6217-22 PMID: 17389404 [PubMed - indexed for MEDLINE]
- Kvansakul M, van Delft MF, Lee EF, Gulbis JM, Fairlie WD, Huang DC, Colman PM. A structural viral mimic of prosurvival Bcl-2: a pivotal role for sequestering proapoptotic Bax and Bak. Mol Cell. 2007 Mar 23;25(6):933-42 PMID: 17386268 [PubMed - indexed for MEDLINE]
- Colman, PM. Anti-influenza drugs from Neuraminidase Inhibitors. Structure-Based Drug Discovery. 2006 Ed RE Hubbard. RSC Publishing, Cambridge UK. 193-218
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Current Laboratory Members
Faculty Member: Peter Colman, BSc(Hons) Adelaide FAA HonDSc Syd PhD Adelaide
Senior Postdoctoral Fellow: Peter Czabotar, BSc PhD Curtin
Research Assistant: Geoff Thompson, BSc(Hons) Melb
Research Assistant: Ahmad Wardak, BSc(Hons) LaT
Administrative Officer: Helen Barry, BA Melb