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

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

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 (US)
Pages (from-to)	540-547.e3
Journal	Structure
Volume	28
Issue number	5
DOIs	https://doi.org/10.1016/j.str.2020.02.005
State	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

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

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

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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.",

keywords = "Francisella tularensis, NMR spectroscopy, X-ray crystallography, computational chemistry, drug discovery, intergrative modeling, molecular biophysics, serial femtosecond crystallography",

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doi = "10.1016/j.str.2020.02.005",

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AU - Zook, James

AU - Shekhar, Mrinal

AU - Hansen, Debra

AU - Conrad, Chelsie

AU - Grant, Thomas

AU - Gupta, Chitrak

AU - White, Thomas

AU - Barty, Anton

AU - Basu, Shibom

AU - Zhao, Yun

AU - Zatsepin, Nadia

AU - Ishchenko, Andrii

AU - Batyuk, Alex

AU - Gati, Cornelius

AU - Li, Chufeng

AU - Galli, Lorenzo

AU - Coe, Jesse

AU - Hunter, Mark

AU - Liang, Meng

AU - Weierstall, Uwe

AU - Nelson, Garret

AU - James, Daniel

AU - Stauch, Benjamin

AU - Craciunescu, Felicia

AU - Thifault, Darren

AU - Liu, Wei

AU - Cherezov, Vadim

AU - Singharoy, Abhishek

AU - Fromme, Petra

PY - 2020/5/5

Y1 - 2020/5/5

N2 - 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.

AB - 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.

KW - Francisella tularensis

KW - NMR spectroscopy

KW - X-ray crystallography

KW - computational chemistry

KW - drug discovery

KW - intergrative modeling

KW - molecular biophysics

KW - serial femtosecond crystallography

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JO - Structure

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

Abstract

Keywords

ASJC Scopus subject areas

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X-ray Structure of Flpp3

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

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Fingerprint

Datasets

X-ray Structure of Flpp3

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