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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 Pseudoenzymes

  • Toxoplasma virulence factor, ROP5 pseudokinase (3q5z and 3q60)
  • 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)
  • the pseudokinase MLKL (4btf) involved in triggering cell death by necroptosis



  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:
  3. Leslie M. Dead or alive? Science. 2013 Apr 5;340(6128):27. doi: 10.1126/science.340.6128.27. PMID:23559233 doi:
  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:

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