Structure of RodA via evolutionary coupling analysis
Andrew Kruse group (Harvard University) and collaborators
Postdoctoral researcher, Megan Sjodt, in the
laboratory of Andrew Kruse at Harvard Medical School, determined the
structure of a bacterial cell wall polymerase, RodA, revealing a highly
conserved, water-filled central cavity that could potentially pave the
way for next-generation broad-spectrum antibacterial therapies. The
structure was phased using a novel evolutionary coupling analysis.
RodA is a member of the SEDS (shape, elongation, division, sporulation)
family of highly conserved essential transmembrane proteins that are
found in nearly all bacteria. Their function was long enigmatic, until
recently when they were found to catalyze the first step in building
the protective bacterial cell wall. The structure of RodA provides the
first molecular insight into how disruption of RodA function causes
bacterial cells to swell and die. This suggests that RodA is a viable
target for the development of small-molecule inhibitors that could be
effective against a wide range of bacterial pathogens.
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Figure: Structure of the transmembrane protein, RodA. |
Citation: Sjodt, M, Brock, K, Dobihal, G, Rohs, PDA,
Green, AG, Hopf, TA, Meeske, AJ, Srisuknimit, V, Kahne, D, Walker, S,
Marks, DS, Bernhardt, TG, Rudner, DZ, Kruse, AC. Structure of
the peptidoglycan polymerase RodA resolved by evolutionary coupling
analysis, Nature 556, 118-121 (2018). DOI:
10.1038/nature25985.
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