Emerging concepts in pseudoenzyme classification, evolution, and signaling.

Emerging concepts in pseudoenzyme classification, evolution, and signaling. Sci Signal. 2019 Aug 13;12(594): Authors: Ribeiro AJM, Das S, Dawson N, Zaru R, Orchard S, Thornton JM, Orengo C, Zeqiraj E, Murphy JM, Eyers PA Abstract The 21st century is witnessing an explosive surge in our understanding of pseudoenzyme-driven regulatory mechanisms in biology. Pseudoenzymes are proteins that have sequence homology with enzyme families but that are proven or predicted to lack enzyme activity due to mutations in otherwise conserved catalytic amino acids. The best-studied pseudoenzymes are pseudokinases, although examples from other families are emerging at a rapid rate as experimental approaches catch up with an avalanche of freely available informatics data. Kingdom-wide analysis in prokaryotes, archaea and eukaryotes reveals that between 5 and 10% of proteins that make up enzyme families are pseudoenzymes, with notable expansions and contractions seemingly associated with specific signaling niches. Pseudoenzymes can allosterically activate canonical enzymes, act as scaffolds to control assembly of signaling complexes and their localization, serve as molecular switches, or regulate signaling networks through substrate or enzyme sequestration. Molecular analysis of pseudoenzymes is rapidly advancing knowledge of how they perform noncatalytic functions and is enabling the discovery of unexpected, and previously unappreciated, functions of th...
Source: Science Signaling - Category: Biomedical Science Authors: Tags: Sci Signal Source Type: research