Figure I. Old Domain, New Tricks.
(A) PKA represents a prototypical protein kinase (PDB ID: 1ATP [113]). The kinase domain is shown as a grey cartoon. Bound ATP and peptide substrates are shown as black and cyan sticks respectively, and Mg2+ ions are shown as brown spheres.
(B) POMK transfers the γ-phosphate from ATP to the mannose unit of glycan-modified α-dystroglycan. The kinase domain is shown as a pale green cartoon. A trisaccharide substrate, colored cyan, traverses the canonical peptide binding site to place the mannose O6 hydroxyl in a phosphoacceptor position next to ATP (present as ADP in the crystal) and the catalytic base aspartate (PDB ID: 5GZ9 [114]).
(C) SelO transfers AMP from ATP onto Ser/Thr/Tyr residues of redox regulatory proteins. The ATP analog AMP-PNP is present in a ‘flipped’ orientation compared to the canonical binding mode in active protein kinases – also seen in the secreted Fam20A pseudokinase [72]. The core kinase domain is colored pale blue, and the SelO-specific sequences are light gray (PDB ID: 6EAC [24]).
(D) The NiRAN domain from nsp12 in the SARS-CoV-2 replication-transcription complex is shown (PDB ID: 6XEZ [92]). The NiRAN domain resembles SelO structurally and in its ‘flipped’ mode of nucleotide binding, with Mg2+-ADP bound in this structure.
(E) The Legionella effector protein SidJ polyglutamylates SidE family ubiquitin ligases during viral amplification. The core pseudokinase domain is shown as a pale pink cartoon, and the SidJ N- and C-terminal domains (NTD and CTD respectively) are colored light yellow (NTD) and gray (CTD). The bound yeast calmodulin (CaM), which activates SidJ, is colored light cyan (PDB ID: 7MIR [23]).