Journal
STRUCTURE
Volume 28, Issue 5, Pages 540-+Publisher
CELL PRESS
DOI: 10.1016/j.str.2020.02.005
Keywords
-
Funding
- U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-76SF00515]
- NIH [P41GM103393]
- NIH Common Fund [R01 GM095583]
- Center for Membrane Proteins in infectious diseases, MPID
- PSI:Biology Structural Biology initiative of the NIH [U54 GM094599]
- Science and Technology Center (STC) BioXFEL'' [STC-1231306]
- Biodesign Center for Applied Structural Discovery at Arizona State University
- SMS at Arizona State University
- CASD at Arizona State University
- Office of Science at DOE [DE-AC05-00OR22725]
- NSF [MCB-1942763]
Ask authors/readers for more resources
Francisella tularensis is the causative agent for the potentially fatal disease tularemia. The lipoprotein Flpp3 has been identified as a virulence determinant of tularemia with no sequence homology outside the Francisella genus. We report a room temperature structure of Flpp3 determined by serial femtosecond crystallo graphy that exists in a significantly different conformation than previously described by the NMR-determined structure. Furthermore, we investigated the conformational space and energy barriers between these two structures by molecular dynamics umbrella sampling and identified three low-energy intermediate states, transitions between which readily occur at room temperature. We have also begun to investigate organic compounds in silico that may act as inhibitors to Flpp3. This work paves the road to developing targeted therapeutics against tularemia and aides in our understanding of the disease mechanisms of tularemia.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available