XFEL and NMR Structures of Francisella Lipoprotein Reveal Conformational Space of Drug Target against Tularemia

James Zook, Mrinal Shekhar, Debra Hansen, Chelsie Conrad, Thomas Grant, Chitrak Gupta, Thomas White, Anton Barty, Shibom Basu, Yun Zhao, Nadia Zatsepin, Andrii Ishchenko, Alex Batyuk, Cornelius Gati, Chufeng Li, Lorenzo Galli, Jesse Coe, Mark Hunter, Meng Liang, Uwe WeierstallGarret Nelson, Daniel James, Benjamin Stauch, Felicia Craciunescu, Darren Thifault, Wei Liu, Vadim Cherezov, Abhishek Singharoy, Petra Fromme

Research output: Contribution to journalArticle

Abstract

Using X-ray free-electron laser (XFEL) technology, Zook et al. describe an alternative protein conformation of the virulence determinant Flpp3 and use molecular dynamics (MD) to investigate conformational landscapes between these conformations. MD identifies several intermediate conformations that allow these conformational transitions to occur at physiologically relevant temperatures and provide insight to potential future drug therapies for the potentially deadly disease tularemia.

Original languageEnglish (US)
Pages (from-to)540-547.e3
JournalStructure
Volume28
Issue number5
DOIs
StatePublished - May 5 2020

Keywords

  • Francisella tularensis
  • NMR spectroscopy
  • X-ray crystallography
  • computational chemistry
  • drug discovery
  • intergrative modeling
  • molecular biophysics
  • serial femtosecond crystallography

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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  • Cite this

    Zook, J., Shekhar, M., Hansen, D., Conrad, C., Grant, T., Gupta, C., White, T., Barty, A., Basu, S., Zhao, Y., Zatsepin, N., Ishchenko, A., Batyuk, A., Gati, C., Li, C., Galli, L., Coe, J., Hunter, M., Liang, M., ... Fromme, P. (2020). XFEL and NMR Structures of Francisella Lipoprotein Reveal Conformational Space of Drug Target against Tularemia. Structure, 28(5), 540-547.e3. https://doi.org/10.1016/j.str.2020.02.005