Pseudoenzyme

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Pseudoenzymes are proteins that cannot catalyze chemical reactions despite being clearly related structurally to functioning enzymes. Many enzyme families contain inactive members. For example, a number of human kinases lack at least one of the key amino acids necessary for catalysis of phosphate transfer [1]. Often pseudoenzymes still have biological roles, albeit non-catalytic. Some assist true enzymes in obtaining functional folds, some server as platforms for other proteins to interact, and some are escorts for proteins [2][3].

3D structures of Pseudoenzymes3D structures of Pseudoenzymes

  • C-terminal domain of splicing factor Prp8p (2og4) resembles an isopeptidase converted to a platform
  • the structure of a fragment of integrin-like kinase (3KMU and 3KMW) demonstrated it is not a kinase and instead serves a structural role linking the cell's cytoskeleton to surface receptors
  • RLCK family member, the Brassinosteroid signaling kinase (4i92, 4i93, 4i94)

RelatedRelated

  • CASK (3c0i, 3c0h, and 3c0g) was originally thought to be a [Pseudoenzyme|pseudoenzyme]], but after the structural was solved it was apparent it could use alternative amino acids in the kinase reaction, see Mukherjee et al., 2008 [4] and Kanaan and Taylor, 2008 [5]

ReferencesReferences

  1. Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S. The protein kinase complement of the human genome. Science. 2002 Dec 6;298(5600):1912-34. PMID:12471243 doi:10.1126/science.1075762
  2. Leslie M. Molecular biology. 'Dead' enzymes show signs of life. Science. 2013 Apr 5;340(6128):25-7. doi: 10.1126/science.340.6128.25. PMID:23559232 doi:http://dx.doi.org/10.1126/science.340.6128.25
  3. Leslie M. Dead or alive? Science. 2013 Apr 5;340(6128):27. doi: 10.1126/science.340.6128.27. PMID:23559233 doi:http://dx.doi.org/10.1126/science.340.6128.27
  4. Mukherjee K, Sharma M, Urlaub H, Bourenkov GP, Jahn R, Sudhof TC, Wahl MC. CASK Functions as a Mg2+-independent neurexin kinase. Cell. 2008 Apr 18;133(2):328-39. PMID:18423203 doi:10.1016/j.cell.2008.02.036
  5. Kannan N, Taylor SS. Rethinking pseudokinases. Cell. 2008 Apr 18;133(2):204-5. doi: 10.1016/j.cell.2008.04.005. PMID:18423189 doi:http://dx.doi.org/10.1016/j.cell.2008.04.005

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