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Review
. 2023 Apr;75(4):370-376.
doi: 10.1002/iub.2698. Epub 2023 Jan 5.

Redefining pseudokinases: A look at the untapped enzymatic potential of pseudokinases

Alex Pon  1 , Adam Osinski  2 , Anju Sreelatha  1   3
Affiliations
Review

Redefining pseudokinases: A look at the untapped enzymatic potential of pseudokinases

Alex Pon et al. IUBMB Life. 2023 Apr.

Abstract

Catalytically inactive kinases, known as pseudokinases, are conserved in all three domains of life. Due to the lack of catalytic residues, pseudokinases are considered to act as allosteric regulators and scaffolding proteins with no enzymatic function. However, since these "dead" kinases are conserved along with their active counterparts, a role for pseudokinases may have been overlooked. In this review, we will discuss the recently characterized pseudokinases Selenoprotein O, Legionella effector SidJ, and the SARS-CoV2 protein nsp12 which catalyze AMPylation, glutamylation, and RNAylation, respectively. These studies provide structural and mechanistic insight into the versatility and diversity of the kinase fold.

Keywords: AMPylation; Legionella; NiRAN; RNA capping; RNAylation; adenylylation; glutamylation; nsp12; oxidative stress; post-translational modification; selenoprotein O; sidJ.

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Figures

FIGURE 1
FIGURE 1
(a) A cartoon representation of Pseudomonas syringae SelO kinase domain (b) a zoomed in view of SelO active site (PDB ID: 6EAC). SelO is shown as orange cartoon, metals are shown as spheres: Magnesium—green, Calcium—Yellow
FIGURE 2
FIGURE 2
(a) A cartoon representation of Legionella pneumophila SidJ kinase (b) a zoomed in view of SidJ active sites (PDB ID: 7MIS). SidJ is shown as blue cartoon, insertion in the catalytic loop is indicated in yellow. Magnesium cations are shown as green spheres. SdeC is shown in magenta
FIGURE 3
FIGURE 3
(a) A cartoon representation of SARS-CoV-2 NiRAN domain (b) a zoomed in view of NiRAN active site (PDB ID: 7CYQ). NiRAN is shown as salmon cartoon, Magnesium metal is shown as a green sphere
See this image and copyright information in PMC

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