Pseudoenzyme

Sidoenzaims bụ ụdị dị iche iche nke enzymes (na-abụkarị protein) nke na-enweghị ihe na-akpali akpali (na-adịghị arụ ọrụ), nke pụtara na ha na-arụ obere ma ọ bụ enweghị enzaim katalisis. ^[1][2] E kwenyere na a na-anọchite anya ha n'Ezinụlọ enzaim niile dị na alaeze nke ndụ, ebe ha nwere ihe mgbaàmà dị mkpa na ọrụ ikerisi nri ọtụtụ n'ime ha na-apụta ìhè ugbu a. Sidoenzaims na-aghọwanye ihe dị mkpa iji nyochaa, ọkachasị dịka nyocha bioinformatics nke genomes na-ekpughe ebe niile ha dị. Ọrụ nchịkwa ha dị mkpa na mgbe ụfọdụ ọrịa na-emetụta n'ụzọ ikerisi nri na nke mgbaàmà na-enyekwa ìhè ọhụrụ na ọrụ ndị na-abụghị nke enzaims na-arụ ọrụ, nke protein moonlighting,^[3][4] imeghari nke protein na ọrụ dị iche iche nke mkpụrụ ndụ (Protin munlaitin). ^[5] A na-atụkwa aro ụzọ ọhụrụ iji lekwasị anya ma kọwaa usoro mgbaàmà mkpụrụ ndụ site n'iji obere mkpụrụ ndụ na ọgwụ. Ihe ndị a na-enyocha nke ọma, na n'ezie pseudoenzymes a kacha ghọta n'ihe gbasara ọrụ mgbaàmà mkpụrụ ndụ bụ ma eleghị anya pseudokinases, pseudoproteases na pseudophosphatases. ^[6][7]'oge na-adịbeghị anya, pseudo-deubiquitylases amalitela ịghọ ihe a ma ama. [1] [2]

Ọdịiche dị na enzaim active and inactive homologues has been noted (and in some cases, understood when comparing catalytically active and inactive proteins residing in recognisable families) for some time at the sequence level,^[8] and some pseudoenzymes have also been referred to as 'prozymes' when they were analysed in protozoan parasites.^[9] The best studied pseudoenzymes reside amongst various key signalling superfamilies of enzymes, such as the proteases,^[10] the protein kinases,^{[11][12][13][14][15][16][17]} protein phosphatases^[18][19] and ubiquitin modifying enzymes.^[20][21] The role of pseudoenzymes as "pseudo scaffolds" has also been recognised ^[22] and pseudoenzymes are now beginning to be more thoroughly studied in terms of their biology and function, in large part because they are also interesting potential targets (or anti-targets) for drug design in the context of intracellular cellular signalling complexes.^[23][24]

1. ↑ (Aug 2019) "Emerging concepts in pseudoenzyme classification, evolution, and signaling". Science Signaling 12 (594): eaat9797. DOI:10.1126/scisignal.aat9797. PMID 31409758. 
2. ↑ (April 2019) "Tracing the origin and evolution of pseudokinases across the tree of life". Science Signaling 12 (578): eaav3810. DOI:10.1126/scisignal.aav3810. PMID 31015289. 
3. ↑ (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. 
4. ↑ (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. 
5. ↑ (November 2016) "The evolving world of pseudoenzymes: proteins, prejudice and zombies". BMC Biology 14 (1): 98. DOI:10.1186/s12915-016-0322-x. PMID 27835992. 
6. ↑ (May 2019) "Metabolic control of BRISC–SHMT2 assembly regulates immune signalling". Nature 570 (7760): 194–199. DOI:10.1038/s41586-019-1232-1. PMID 31142841. 
7. ↑ (Feb 2018) "Pseudo-DUBs as allosteric activators and molecular scaffolds of protein complexes.". Biochem Soc Trans 46 (2): 453–466. DOI:10.1042/BST20160268. PMID 29472364. 
8. ↑ (October 2002) "Sequence and structural differences between enzyme and nonenzyme homologs". Structure 10 (10): 1435–51. DOI:10.1016/s0969-2126(02)00861-4. PMID 12377129. 
9. ↑ (May 2007) "Allosteric regulation of an essential trypanosome polyamine biosynthetic enzyme by a catalytically dead homolog". Proceedings of the National Academy of Sciences of the United States of America 104 (20): 8275–80. DOI:10.1073/pnas.0701111104. PMID 17485680. 
10. ↑ (July 2012) "New lives for old: evolution of pseudoenzyme function illustrated by iRhoms". Nature Reviews. Molecular Cell Biology 13 (8): 489–98. DOI:10.1038/nrm3392. PMID 22781900. 
11. ↑ (April 2019) "Tracing the origin and evolution of pseudokinases across the tree of life". Science Signaling 12 (578): eaav3810. DOI:10.1126/scisignal.aav3810. PMID 31015289. 
12. ↑ (December 2002) "The protein kinase complement of the human genome". Science 298 (5600): 1912–34. DOI:10.1126/science.1075762. PMID 12471243. 
13. ↑ (September 2006) "Emerging roles of pseudokinases". Trends in Cell Biology 16 (9): 443–52. DOI:10.1016/j.tcb.2006.07.003. PMID 16879967. 
14. ↑ (April 2017) "Tribbles in the 21st Century: The Evolving Roles of Tribbles Pseudokinases in Biology and Disease". Trends in Cell Biology 27 (4): 284–298. DOI:10.1016/j.tcb.2016.11.002. PMID 27908682. 
15. ↑ (September 2014) "Day of the dead: pseudokinases and pseudophosphatases in physiology and disease". Trends in Cell Biology 24 (9): 489–505. DOI:10.1016/j.tcb.2014.03.008. PMID 24818526. 
16. ↑ (September 2013) "The pseudokinase MLKL mediates necroptosis via a molecular switch mechanism". Immunity 39 (3): 443–53. DOI:10.1016/j.immuni.2013.06.018. PMID 24012422. 
17. ↑ (August 1998) "Gathering STYX: phosphatase-like form predicts functions for unique protein-interaction domains". Trends in Biochemical Sciences 23 (8): 301–6. DOI:10.1016/s0968-0004(98)01241-9. PMID 9757831. 
18. ↑ (September 2014) "Day of the dead: pseudokinases and pseudophosphatases in physiology and disease". Trends in Cell Biology 24 (9): 489–505. DOI:10.1016/j.tcb.2014.03.008. PMID 24818526. 
19. ↑ (April 2017) "Genomics and evolution of protein phosphatases". Science Signaling 10 (474): eaag1796. DOI:10.1126/scisignal.aag1796. PMID 28400531. 
20. ↑ (September 2015) "Higher-Order Assembly of BRCC36-KIAA0157 Is Required for DUB Activity and Biological Function". Molecular Cell 59 (6): 970–83. DOI:10.1016/j.molcel.2015.07.028. PMID 26344097. 
21. ↑ (April 2017) "Roles of the TRAF6 and Pellino E3 ligases in MyD88 and RANKL signaling". Proceedings of the National Academy of Sciences of the United States of America 114 (17): E3481–E3489. DOI:10.1073/pnas.1702367114. PMID 28404732. 
22. ↑ (April 2017) "Pseudoscaffolds and anchoring proteins: the difference is in the details". Biochemical Society Transactions 45 (2): 371–379. DOI:10.1042/bst20160329. PMID 28408477. 
23. ↑ (October 2015) "Tribbles pseudokinases: novel targets for chemical biology and drug discovery?". Biochemical Society Transactions 43 (5): 1095–103. DOI:10.1042/bst20150109. PMID 26517930. 
24. ↑ (January 2017) "Pseudokinases: update on their functions and evaluation as new drug targets". Future Medicinal Chemistry 9 (2): 245–265. DOI:10.4155/fmc-2016-0207. PMID 28097887.