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 Weierstall; Garret Nelson; Daniel James; Benjamin Stauch; Felicia Craciunescu; Darren Thifault; Wei Liu; Vadim Cherezov; Abhishek Singharoy; Petra Fromme

doi:10.1016/j.str.2020.02.005

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

Arizona State University

Research output: Contribution to journal › Article

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 language	English
Pages (from-to)	540-547.e3
Journal	Structure
Volume	28
Issue number	5
DOIs	https://doi.org/10.1016/j.str.2020.02.005
Publication status	Published - 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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10.1016/j.str.2020.02.005

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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

XFEL and NMR Structures of Francisella Lipoprotein Reveal Conformational Space of Drug Target against Tularemia. / Zook, James; Shekhar, Mrinal; Hansen, Debra; Conrad, Chelsie; Grant, Thomas; Gupta, Chitrak; White, Thomas; Barty, Anton; Basu, Shibom; Zhao, Yun; Zatsepin, Nadia; Ishchenko, Andrii; Batyuk, Alex; Gati, Cornelius; Li, Chufeng; Galli, Lorenzo; Coe, Jesse; Hunter, Mark; Liang, Meng; Weierstall, Uwe; Nelson, Garret; James, Daniel; Stauch, Benjamin; Craciunescu, Felicia; Thifault, Darren; Liu, Wei; Cherezov, Vadim; Singharoy, Abhishek; Fromme, Petra.

In: Structure, Vol. 28, No. 5, 05.05.2020, p. 540-547.e3.

Research output: Contribution to journal › Article

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, Weierstall, U, Nelson, G, James, D, Stauch, B, Craciunescu, F, Thifault, D, Liu, W, Cherezov, V, Singharoy, A & Fromme, P 2020, 'XFEL and NMR Structures of Francisella Lipoprotein Reveal Conformational Space of Drug Target against Tularemia', Structure, vol. 28, no. 5, pp. 540-547.e3. https://doi.org/10.1016/j.str.2020.02.005

Zook, James ; Shekhar, Mrinal ; Hansen, Debra ; Conrad, Chelsie ; Grant, Thomas ; Gupta, Chitrak ; White, Thomas ; Barty, Anton ; Basu, Shibom ; Zhao, Yun ; Zatsepin, Nadia ; Ishchenko, Andrii ; Batyuk, Alex ; Gati, Cornelius ; Li, Chufeng ; Galli, Lorenzo ; Coe, Jesse ; Hunter, Mark ; Liang, Meng ; Weierstall, Uwe ; Nelson, Garret ; James, Daniel ; Stauch, Benjamin ; Craciunescu, Felicia ; Thifault, Darren ; Liu, Wei ; Cherezov, Vadim ; Singharoy, Abhishek ; Fromme, Petra. / XFEL and NMR Structures of Francisella Lipoprotein Reveal Conformational Space of Drug Target against Tularemia. In: Structure. 2020 ; Vol. 28, No. 5. pp. 540-547.e3.

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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.",

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AU - Fromme, Petra

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