Pseudoenzymes are variants of enzymes that are catalytically-deficient (usually inactive), meaning that they perform little or no enzyme catalysis. [1] They are believed to be represented in all major enzyme families in the kingdoms of life, where they have important signaling and metabolic functions, many of which are only now coming to light.[2] Pseudoenzymes are becoming increasingly important to analyse, especially as the bioinformatic analysis of genomes reveals their ubiquity. Their important regulatory and sometimes disease-associated functions in metabolic and signalling pathways are also shedding new light on the non-catalytic functions of active enzymes, of moonlighting proteins,[3][4] the re-purposing of proteins in distinct cellular roles (Protein moonlighting). They are also suggesting new ways to target and interpret cellular signalling mechanisms using small molecules and drugs.[5] The most intensively analyzed, and certainly the best understood pseudoenzymes in terms of cellular signalling functions are probably the pseudokinases, the pseudoproteases and the pseudophosphatases. Recently, the pseudo-deubiquitylases have also begun to gain prominence.[6][7]
- ^ Ribeiro AJ, Das S, Dawson N, Zaru R, Orchard S, Thornton JM, Orengo C, Zeqiraj E, Murphy JM, Eyers PA (Aug 2019). "Emerging concepts in pseudoenzyme classification, evolution, and signaling". Science Signaling. 12 (594): eaat9797. doi:10.1126/scisignal.aat9797. PMID 31409758.
- ^ Kwon A, Scott S, Taujale R, Yeung W, Kochut KJ, Eyers PA, Kannan N (April 2019). "Tracing the origin and evolution of pseudokinases across the tree of life". Science Signaling. 12 (578): eaav3810. doi:10.1126/scisignal.aav3810. PMC 6997932. PMID 31015289.
- ^ Jeffery CJ (Feb 2019). "The demise of catalysis, but new functions arise: pseudoenzymes as the phoenixes of the protein world". Biochemical Society Transactions. 47 (1): 371–379. doi:10.1042/BST20180473. PMID 30710059. S2CID 73437705.
- ^ Jeffery CJ (Dec 2019). "Multitalented actors inside and outside the cell: recent discoveries add to the number of moonlighting proteins". Biochemical Society Transactions. 47 (6): 1941–1948. doi:10.1042/BST20190798. PMID 31803903. S2CID 208643133.
- ^ Eyers PA, Murphy JM (November 2016). "The evolving world of pseudoenzymes: proteins, prejudice and zombies". BMC Biology. 14 (1): 98. doi:10.1186/s12915-016-0322-x. PMC 5106787. PMID 27835992.
- ^ Walden M, Masandi SK, Pawlowski K, Zeqiraj E (Feb 2018). "Pseudo-DUBs as allosteric activators and molecular scaffolds of protein complexes" (PDF). Biochem Soc Trans. 46 (2): 453–466. doi:10.1042/BST20160268. PMID 29472364. S2CID 3477709.
- ^ Walden M, Tian L, Ross RL, Sykora UM, Byrne DP, Hesketh EL, Masandi SK, Cassel J, George R, Ault JR, El Oualid F, Pawłowski K, Salvino JM, Eyers PA, Ranson NA, Del Galdo F, Greenberg RA, Zeqiraj E (May 2019). "Metabolic control of BRISC–SHMT2 assembly regulates immune signalling" (PDF). Nature. 570 (7760): 194–199. Bibcode:2019Natur.570..194W. doi:10.1038/s41586-019-1232-1. PMC 6914362. PMID 31142841.