The Traveller's Last Journey DEDICATED TO SHAI MAROM Z"L

Science Review: Pseudoenzymes

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Concepts: Psudeoenzymes

Source: A News Focus piece in Science (April 5, 2013).

  • History: A 2002 study found that of 518 human protein kinases encoded in the DNA, about 10% lack at least one of three amino acids necessary for phosphate transfer. This was the first time the magnitude of the phenomenon was appreciated.
  • Likely mechanisms for creation: (1) duplication of enzyme’s gene followed by loss of catalytic function; and (2) duplication followed by a gain of catalytic ability (which is likely less common). That these are not merely degraded sequences is proven by the fact that evolutionary lineages show them to be undergoing conservation.
  • Common molecular functions include their (often: retained) ability to bind to their active kin enzyme (or its binding partners, including target proteins). Thus can form protein platforms to regulate kin enzymes (by associating proteins, by bringing into an active conformation, by translocating).
  • Interesting organism function: Mice block Toxoplasma with IRG proteins, which the parasite counters with ROP18 and pseudo-enzyme ROP5 proteins. There are many ROP5 proteins; it makes sense for the parasite to mutate ROP5 (and not ROP18) in its arms race against IRG, since ROP5 is more resilient to mutations whilst maintaining its function, than ROP18 whose catalytic function is relatively vulnerable.
  • An implication: Tantalizing drug targets, but little research yet.
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The Traveller's Last Journey DEDICATED TO SHAI MAROM Z"L

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