@article{5f5398fda6654f3f90c600687f6cf59e,
title = "XFEL and NMR Structures of Francisella Lipoprotein Reveal Conformational Space of Drug Target against Tularemia",
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",
author = "James Zook and Mrinal Shekhar and Debra Hansen and Chelsie Conrad and Thomas Grant and Chitrak Gupta and Thomas White and Anton Barty and Shibom Basu and Yun Zhao and Nadia Zatsepin and Andrii Ishchenko and Alex Batyuk and Cornelius Gati and Chufeng Li and Lorenzo Galli and Jesse Coe and Mark Hunter and Meng Liang and Uwe Weierstall and Garret Nelson and Daniel James and Benjamin Stauch and Felicia Craciunescu and Darren Thifault and Wei Liu and Vadim Cherezov and Abhishek Singharoy and Petra Fromme",
note = "Funding Information: Use of LCLS, SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under contract no. DE-AC02-76SF00515. Parts of the sample injector used at LCLS for this research were funded by the NIH, P41GM103393, formerly P41RR001209. This work was supported by the NIH Common Fund Grant R01 GM095583 (to P.F.) and the Center for Membrane Proteins in infectious diseases, MPID supported by the PSI:Biology Structural Biology initiative of the NIH U54 GM094599. We also acknowledge funding from the Science and Technology Center (STC) “BioXFEL” through award STC-1231306. The work was also supported by funds from the Biodesign Center for Applied Structural Discovery at Arizona State University. A.S. and C.G. acknowledge start-up funds from the SMS and CASD at Arizona State University, and the resources of the OLCF at the Oak Ridge National Laboratory, which is supported by the Office of Science at DOE under Contract No. DE-AC05-00OR22725, made available via the INCITE program. AS acknowledges CAREER award from NSF (MCB-1942763). Conceptualization, J.Z. P.F. and A.S.; Methodology, J.Z. P.F. D.H. A.S. C.C. F.C. T.G. and M.S.; Software, T.W. A.Barty. M.S. J.Z. Y.Z. N.Z. A.I. A.Batyuk. and C.L.; Validation, T.G. S.B. J.Z. C.Gupta, M.S. and D.T.; Formal Analysis, T.G. J.Z. M.S. S.B. and A.Batyuk.; Investigation, J.Z. M.S. C.C. T.G. C.Gati. J.C. G.N. D.J. F.C. L.G. B.S. and D.T.; Resources, V.C. A.S. M.H. M.L. and U.W.; Data Curation, S.B. J.Z. A.Barty. and M.S.; Writing – Original Draft, J.Z. P.F. A.S. M.S. D.H. and F.C.; Writing – Review & Editing, J.Z. P.F. A.S. D.H. B.S. J.C. V.C. and W.L.; Visualization, J.Z. P.F. A.S. M.S. and C. Gupta.; Supervision, V.C. W.L. P.F. A.S. and J.Z.; Project Administration, J.Z. P.F. and A.S.; Funding Acquisition, P.F. The authors declare no competing interests. Funding Information: Use of LCLS, SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy , Office of Science, Office of Basic Energy Sciences under contract no. DE-AC02-76SF00515. Parts of the sample injector used at LCLS for this research were funded by the NIH , P41GM103393 , formerly P41RR001209. This work was supported by the NIH Common Fund Grant R01 GM095583 (to P.F.) and the Center for Membrane Proteins in infectious diseases , MPID supported by the PSI:Biology Structural Biology initiative of the NIH U54 GM094599 . We also acknowledge funding from the Science and Technology Center (STC) “BioXFEL” through award STC-1231306. The work was also supported by funds from the Biodesign Center for Applied Structural Discovery at Arizona State University . A.S. and C.G. acknowledge start-up funds from the SMS and CASD at Arizona State University, and the resources of the OLCF at the Oak Ridge National Laboratory , which is supported by the Office of Science at DOE under Contract No. DE-AC05-00OR22725 , made available via the INCITE program. AS acknowledges CAREER award from NSF ( MCB-1942763 ). Publisher Copyright: {\textcopyright} 2020",
year = "2020",
month = may,
day = "5",
doi = "10.1016/j.str.2020.02.005",
language = "English (US)",
volume = "28",
pages = "540--547.e3",
journal = "Structure",
issn = "0969-2126",
publisher = "Cell Press",
number = "5",
}