Allingham, John - Queen's University - Department of Biomedical and Molecular Sciences

个人简介

Education: B.Sc. (Hons.) in Biochemistry (1996) - The University of Western Ontario Ph.D. in Biochemistry and Molecular Biology (2002) - The University of Western Ontario CIHR Postdoctoral Fellow in Structural Biology (2002-2006) - Department of Biochemistry, University of Wisconsin Current Funding: Canadian Institutes of Health Research Natural Sciences and Engineering Research Council Canada Research Chairs Program

研究领域

Structure-function relationships in kinesin motor proteins Roles of kinesins in mitotic spindle function and cell shape changes in human fungal pathogens and cancer cells Molecular recognition of protein surfaces and perturbation of protein function by natural toxic small molecules Protein engineering and drug design A primary goal of the research in my lab is to understand the mechanisms of action of biomolecules, and, where possible, to rationally alter or re-purpose their functions in useful ways. To do this, we use X-ray crystallography, high-resolution microscopy, and a number of other biophysical tools to gain detailed descriptions of these molecules in solution and inside cells. Our most intensive areas of focus in recent years has been on: (1) kinesin motor proteins, which form a large superfamily of cytoskeletal motors that are essential for cellular cargo transport, cell division, and cell shape changes; and (2) on natural toxins that possess anti-fungal and anti-tumor properties. The activites these molecules possess have direct relevance for biomedicine. They also provide frameworks for understanding the fundamental underpinnings of biomolecule design.

近期论文

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Brockhausen I, Nair DG, Chen M, Yang X, Allingham JS, Szarek WA, Anastassiades T. Human acetyl-CoA:glucosamine-6-phosphate N-acetyltransferase 1 has a relaxed donor specificity and transfers acyl groups up to four carbons in length. Biochem Cell Biol. 2016 Apr;94(2):197-204. PMID: 26935656 Frazer, C., Joshi, M., Delorme, C., Davis, D., Bennett, R.J., Allingham, J.S. Candida albicans kinesin Kar3 depends on a Cik1-like regulatory partner protein for its roles in mating, cell morphogenesis and bipolar spindle formation, Eukaryotic Cell, 2015 Aug 14(8):755-74. PMID: 26024903 Arora, K., Talje, L., Asenjo, A.B., Andersen, P., Atchia, K., Joshi, M., Sosa, H., Allingham, J.S., Kwok, B.H. (2014) KIF14 Binds tightly to microtubules and adopts a rigor-like conformation. J. Mol. Biol. 2014 Aug 26;426(17):2997-3015. PMID: 24949858 Partha, S.K., Ravulapalli, R., Allingham, J.S., Campbell, R.L., Davies, P.L. (2014) Crystal structure of calpain-3 penta-EF-hand (PEF) domain - a homodimerized PEF family member. FEBS J. 2014 Jul;281(14):3138-49. PMID: 24846670 Sun, T., Lin, F.H., Campbell, R.L., Allingham, J.S., Davies, P.L. (2014) An antifreeze protein folds with an interior network of more than 400 semi-clathrate waters. Science 2014 Feb 14;343(6172):795-8. PMID: 24531972 Joshi, M., Duan, D., Drew, D., Jia, Z., Davis, D., Campbell, R.L., Allingham, J.S. (2013) Kar3Vik1 Mechanochemistry Is Inhibited by Mutation or Deletion of the C Terminus of the Vik1 Subunit. J. Biol. Chem. 2013 Dec 27;288(52):36957-70. PMID: 24240171 Guo, S., Garnham, C.P., Karunan Partha, S., Campbell, R.L., Allingham, J.S., Davies, P.L. (2013) Role of Ca²⁺ in folding the tandem β-sandwich extender domains of a bacterial ice-binding adhesin. FEBS J. 2013 Nov;280(22):5919-32. PMID: 24024640 Delorme, C., Joshi, M. & Allingham, J.S. (2012) Crystal structure of the Candida albicans Kar3 kinesin motor domain fused to maltose-binding protein. Biochem. Biophys. Res. Commun. 2012 Nov 30;428(4):427-32. PMID: 23137538 Duan, D., Jia, Z., Joshi, M., Brunton, J., Chan, M., Drew, D., Davis, D. & Allingham, J.S. (2012) Neck rotation and neck mimic docking in the non-catalytic Kar3-associated protein Vik1. J. Biol. Chem. Nov 23;287(48):40292-301. PMID: 23043140 Kwok, E., Everingham, S., Zhang, S., Greer, P.A., Allingham. J.S., & Craig, A.W. (2012) FES Kinase Promotes Mast Cell Recruitment to Mammary Tumors Via the Stem Cell Factor/KIT Receptor Signaling Axis. Mol. Cancer Res. 2012 Jul;10(7):881-91. PMID: 22589410 Duan, D., Hnatchuk, D., Brenner, J. Davis, D., & Allingham, J.S. (2012) Crystal structure of the Kar3-like kinesin motor domain from the filamentous fungus Ashbya gossypii. Proteins 2012 Apr;80(4):1016-27. PMID: 22493778 Stark, B.C., Wen, K.K., Allingham, J.S., Rubenstein, P.A., & Lord, M. (2011) Functional adaptation between yeast actin and its cognate myosin motors, J. Biol. Chem. 2011 Sep 2;286(35):30384-92. PMID: 21757693 Xu, C., Liu, B., Han, Y., Feng, L. Allingham, J.S., Szarek, W.A., Wang, L., & Brockhausen, I. (2011) Biochemical Characterization of UDP-Gal:GlcNAc-pyrophosphate-lipid Beta-1,4-Galactosyltransferase WfeD, a new enzyme from Shigella boydii type 14 that catalyses the second step in O-antigen repeating-unit synthesis. J. Bacteriol. 2011 Jan;193(2):449-59. PMID: 21057010 Blain, J. C., Mok, Y-F., Kubanek, J. & Allingham, J. S. (2010) Two Molecules of Lobophorolide Cooperate to Stabilize an Actin Dimer Using Both Their 'Ring' and 'Tail' Region. Chem. Biol. 2010 Aug 27;17(8):802-7. PMID: 20797609 Klein, J. C., Svensson, B., Burr, A. R., Kennedy, D. J., Allingham, J. S., Titus, M. A., Rayment, I. & Thomas, D. D. (2008) Actin-binding cleft closure in myosin II probed by site-directed spin labeling and pulsed EPR. Proc. Natl. Acad. Sci. USA 2008 Sep 2;105(35):12867-72. PMID: 18725645 Lucas-lopez, C. Allingham, J. S., Leb, T., Lawson, C. P., Brenk, R. Sellers, J. R., Rayment, I. & Westwood, N. J. (2008) The small molecule tool (s)-(-)-Blebbistatin: novel insights of relevance to myosin inhibitor design. Org. Biomol. Chem. 2008 Jun 21;6(12):2076-84. PMID: 18528569 Tanaka, J. Blain, J. C. & Allingham, J. S. (2008) Actin-binding toxin 'tail' wags the dog. Chem. Biol. 2008 Mar;15(3):205-7. PMID:18355717 Allingham, J.S., Miles, C.O., & Rayment, I. (2007) A Structural Basis for Regulation of Actin Polymerization by Pectenotoxins. J. Mol. Biol. 2007 Aug 24;371(4):959-70. PMID: 17599353 Allingham, J.S., Sproul, L.R., Rayment, I. & Gilbert, S.P. (2007) Vik1 Modulates Microtubule-Kar3 Interactions Through a Motor Domain That Lacks an Active Site. Cell 2007 Mar 23;128(6):1161-72. PMID: 17382884 Rayment, I. & Allingham, J.S. (2007) Myosin Motors: The Chemical Restraints Imposed by ATP. Lecture Notes in Physics 711, 15-40. (Book Chapter) Allingham, J. S., Klenchin, V. A., & Rayment, I. (2006) Actin-Targeting Natural Products: Structures, Properties and Mechanisms of Action. Cell. Mol. Life Sci. 2006 Sep;63(18):2119-34. PMID: 16909206 Allingham, J. S., Zampella, A., D'Auria,, M. V., & Rayment, I. (2005) Structures of microfilament destabilizing toxins bound to actin provide insight into toxin design and activity. Proc. Natl. Acad. Sci. USA 2005 Oct 11;102(41):14527-32. PMID: 16192358 Allingham, J. S., Smith, R., & Rayment, I. (2005) The structural basis of blebbistatin inhibition and specificity for myosin II. Nat. Struct. Mol. Biol. 2005 Apr;12(4):378-9. PMID: 15750603