Fig. 1.

Pseudoenzymes can allosterically regulate a partner protein’s catalytic activity. a The pseudo-deubiquitinase (DUB), KIAA0157 (yellow), which lacks a canonical Zn-binding motif (residues shown as sticks and labelled), binds to the canonical DUB, BRCC36 (blue), to promote its DUB activity. BRCC36 binds Zn²⁺ (grey sphere) via the labelled residues (shown as blue sticks). The KIAA0157–BRCC36 heterodimeric complex assembles into a higher order “superdimer”, which is an active DUB. PDB accession 5CW3 [11]. b The pseudokinase domain of HER3 (yellow) binds ‘head-to-tail’ and allosterically regulates the activation of the conventional protein tyrosine kinase EGFR (blue). While each domain can accommodate and bind to a nucleotide (cyan) and a divalent cation (grey spheres), HER3 exhibits defective catalytic activity owing to substitution of the catalytic Asp acid residue to an Asn at position 815 (yellow sticks). In contrast, EGFR contains conventional catalytic residues (blue sticks, labelled), which allow it to phosphorylate substrates on tyrosine residues. PDB accession 4RIW [31]. Cartoons were drawn using Pymol