Cucumber mosaic virus (CMV) is an insect-transmitted virus that modifies interactions between its infected host plants and its aphid vectors in ways that increase the probability of transmission over various ranges and timescales (Donnelly et al., 2019; Carr et al., 2020). CMV does not infect its aphid vectors but influences their behaviour by altering the biochemistry of infected host plants. The paradigmatic example of this phenomenon is the interaction of the aphids Aphis gossypii and Myzus persicae with Cucurbita pepo plants infected with the Fny strain of CMV (Fny-CMV) (Mauck et al., 2010). CMV infection causes infected cucurbits to emit a mix of volatile organic compounds that attract aphids, but infection also induces accumulation of antixenotic, that is, feeding-deterrent, compounds in the leaves that ensure that aphids feed for only a brief time before moving to another plant (Mauck et al., 2010; Carmo-Souza et al., 2014). Because CMV is a nonpersistently transmitted virus (virus particles acquired from an infected plant are attached loosely to an aphid's stylet mouthparts), this short feed is sufficient to render the aphids competent to transmit infection to neighbouring hosts (Krenz et al., 2015).

Mitochondrial endonuclease G from Leishmania infantum (LiEndoG) participates in the degradation of double-stranded DNA (dsDNA) during parasite cell death and is catalytically inactive at a pH of 8.0 or above. The presence, in the primary sequence, of an acidic amino acid-rich insertion exclusive to trypanosomatids and its spatial position in a homology-built model of LiEndoG led us to postulate that this peptide stretch might act as a pH sensor for self-inhibition. We found that a LiEndoG variant lacking residues 145–180 is indeed far more active than its wild-type counterpart at pH values >7.0. In addition, we discovered that (i) LiEndoG exists as a homodimer, (ii) replacement of Ser211 in the active-site SRGH motif with the canonical aspartate from the DRGH motif of other nucleases leads to a catalytically deficient enzyme, (iii) the activity of the S211D variant can be restored upon the concomitant replacement of Ala247 with Arg and (iv) a C-terminal extension is responsible for the observed preferential cleavage of single-stranded DNA (ssDNA) and ssDNA–dsDNA junctions. Taken together, our results support the view that LiEndoG is a multidomain molecular machine whose nuclease activity can be subtly modulated or even abrogated through architectural changes brought about by environmental conditions and interaction with other binding partners.

Lithium ion, commonly used as the carbonate salt in the treatment of bipolar disorders, has been identified as an inhibitor of several kinases, including Glycogen Synthase Kinase‐3β, for almost 20 years. However, both the exact mechanism of enzymatic inhibition and its apparent specificity for certain metalloenzymes are still a matter of debate. A data‐driven hypothesis is presented that accounts for the specificity profile of kinase inhibition by lithium in terms of the presence of a unique protein environment in the magnesium‐binding site. This hypothesis has been validated by the discovery of two novel potential targets for lithium, namely NEK3 and MOK, which are related to neuronal function.