TY - JOUR
T1 - XFEL and NMR Structures of Francisella Lipoprotein Reveal Conformational Space of Drug Target against Tularemia
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
N1 - 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 ).
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
UR - http://www.scopus.com/inward/record.url?scp=85083862415&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85083862415&partnerID=8YFLogxK
U2 - 10.1016/j.str.2020.02.005
DO - 10.1016/j.str.2020.02.005
M3 - Article
C2 - 32142641
AN - SCOPUS:85083862415
VL - 28
SP - 540-547.e3
JO - Structure with Folding & design
JF - Structure with Folding & design
SN - 0969-2126
IS - 5
ER -