Photo of Michael S. Chapman, Ph.D.

Michael S. Chapman Ph.D.

  •      (503) 494-1025
    • Professor of Biochemistry and Molecular Biology School of Medicine
    • Interim Chair Biochemistry and Molecular Biology School of Medicine
    • Richard T. Jones Chair of Structural Biology Biochemistry and Molecular Biology School of Medicine
    • Director, Quantitative Bioscience training program
    • Biochemistry and Molecular Biology Graduate Program School of Medicine
    • Program in Molecular and Cellular Biosciences School of Medicine

Atomic structure, interactions and dynamics are core to understanding bio-molecular mechanism. The Chapman group uses an array of physical and biological experiments to build and refine computational models of molecular structure-dynamics that explain function.

Using X-ray crystallography, we have determined the atomic structure of adeno-associated virus (AAV), a leading DNA-delivery vector for treating genetic diseases by gene therapy. We have recently screened the human genome for genes essential to AAV's cellular entry, identifying a recycling receptor in host cells that is needed for productive viral entry and trafficking towards the nucleus. Electron microscopy is now at the center of efforts to map, in atomic details, the interactions of host proteins with AAV as it enters the cell, preparing a foundation for modulating the specificity of the virus.

Protein motions are often overlooked, because they are difficult to characterize, but they are often critical to function. The rate-limiting millisecond dynamics of arginine kinase provide a window through which we are learning general principles. NMR measurements of local exchange rates are combined with crystallographic structure to model the mechanics of protein dynamics through the reaction cycle of an enzyme. It is providing the first experimental evidence in support of theories predicting heightened, rather than lessened protein dynamics in the transition state. We are now characterizing their nature and relation to intrinsic modes of motion that have evolved in enzymes.

 

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Areas of interest

  • Viral-host interactions. Enzyme dynamics. Biophysics. Structural Biology.

Education

  • B.Sc., University of London, Kings College, London United Kingdom 1982
  • M.Sc., University of London, Birkbeck College, London United Kingdom 1983
  • Ph.D., University of California, Los Angeles, Los Angeles California 1987

Honors and awards

  • Fellow, American Association for the Advancement of Science

Memberships and associations

  • Knight Cancer Institute Member
  • American Crystallography Association
  • American Society for Gene & Cell Therapy
  • American Society for Virology
  • Protein Society

Publications

  • Chapman, M., Suh, S. W., Cascio, D., Smith, W. W. & Eisenberg, D. (1987). Sliding-layer conformational change limited by quaternary structure in plant RuBisCO. Nature 329, 354-356. PMID: 3627277.

  • Chapman, M. S., Suh, S. W., Curmi, P. M. G., Cascio, D., Smith, W. W. & Eisenberg, D. S. (1988). Tertiary Structure of Plant RuBisCO: Domains and their Contacts. Science 241, 71-74. PMID: 3133767.

  • Tsao, J., Chapman, M. S., Agbandje, M., Keller, W., Smith, K., Wu, H., Luo, M., Smith, T. J., Rossmann, M. G., Compans, R. W. & Parrish, C. (1991). The Three-Dimensional Structure of Canine Parvovirus and its Functional Implications. Science 251, 1456-1464. PMID: 2006420.

  • Zhou, G., Somasundaram, T., Blanc, E., Parthsarathy, G., Ellington, W. R. & Chapman, M. S. (1998). Transition state structure of arginine kinase: Implications for catalysis of bimolecular reactionsProc Natl Acad Sci, USA 95, 8449-54. PMID: 9671698.

  • Xie, Q., Bu, W., Bhatia, S., Hare, J., Somasundaram, T., Azzi, A., and Chapman, M.S. 2002. The atomic structure of adeno-associated virus (AAV-2), a vector for human gene therapy. Proc Natl Acad Sci, USA 99: 10405-10410. PMID: 12136130.

  • Chapman, M.S., A. Trzynka, and B.K. Chapman (2013), Atomic Modeling of cryo-Electron Microscopy Reconstructions - Joint refinement of Model and Imaging Parameters. Journal of Structural Biology 182:10-21. PMID 23376441.

  • Chapman, B.K., Davulcu, O., Skalicky, J.J., Br?schweiler, R.P. and Chapman, M.S. (2015). Parsimony in Protein Conformational Change, Structure, 23: 1190-1198. doi:10.1016/j.str.2015.05.011.

  • Pillay, S¹., Meyer, N.L.¹, Puschnik, A.S., Davulcu, O., Diep, J., Ishikawa, Y., Jae, L.T., Wosen, J.E., Nagamine, C.M., Chapman, M.S.², and Carette, J.E.² (2016). An essential receptor for adeno-associated virus infection. Nature 530, 108-112. ¹Co-1st / ²corresopnding authors. doi:10.1038/nature16465.

  • Xie, Q., Noble, A.J., Sousa, D.R., Meyer, N.L., Davulcu, O., Zhang, F., Linhardt, R.J., Stagg, S.M., Chapman, M.S. (2017). The 2.8 Å Electron Microscopy Structure of Adeno-Associated Virus-DJ Bound by a Heparanoid Pentasaccharide. Mol. Ther. Methods Clin. Dev. 5: 1-12. doi:10.1016/j.omtm.2017.02.004.

  • Peng,Y., Hansen, A.L., Bruschweiler-Li, L., Davulcu, O., Skalicky, J.J., Chapman, M.S. and Brüschweiler, R.P. (2017). The Michaelis Complex of Arginine Kinase Samples the Transition State at a Frequency that Matches the Catalytic Rate. J. Am. Chem. Soc., 139: 4846-4853; doi:10.1021/jacs.7b00236 PMID: 28287709.

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