Abstract
FIC domain containing proteins (Fic proteins) are present in all domains of life but particularly widespread among prokaryotes. FIC domains with a fully conserved HxFx[D/E]GNGRxxR active site motif catalyze adenylylation (also known as AMPylation), the transfer of an adenosine 5′-monophosphate moiety onto target proteins. Adenylylation activity is tightly controlled by an inhibitory α-helix (α inh) that can either be part of the Fic protein (intramolecular inhibition) or encoded on a different polypeptide chain (intermolecular inhibition), the latter constituting a novel class of type II toxin-antitoxin (TA) modules represented by VbhT-VbhA of Bartonella schoenbuchensis and FicT-FicA of Escherichia coli. The helix α inh harbors a [S/T]xxxE[G/N] motif with the conserved glutamate partially obstructing the ATP-binding site and forcing ATP to bind in a catalytically incompetent conformation. Release of inhibition by removal of the antitoxin component or by mutation of the conserved glutamate in α inh converts Fic proteins into toxins that severely impair bacterial growth.
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Goepfert, A., Harms, A., Schirmer, T., Dehio, C. (2013). Type II Toxin-Antitoxin Loci: The fic Family. In: Gerdes, K. (eds) Prokaryotic Toxin-Antitoxins. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-33253-1_10
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DOI: https://doi.org/10.1007/978-3-642-33253-1_10
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