New Biology from Natural Metamorphosis of a Conventional Class of Enzymes
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A group of enzymes known as aminoacyl tRNA synthetases interpret genetic information through catalysis of aminoacylation reactions that establish the genetic code. Errors of interpretation are corrected by a universal mechanism that is facilitated by novel domains incorporated into these same enzymes. This error-correcting activity is closely associated with the beginnings of living organism, and defects in this activity lead to disease and even lethality. The paradigm of incorporating novel domain additions to develop a specialized activity has been expanded in higher organisms where these domain additions are incorporated into a large library of naturally occurring new structures arising from alternative splicing and proteolysis. This metamorphosis into new structures gives rise to a diversity of new functions that go beyond translation of genetic information. Investigations of several of these structural metamorphs have uncovered new biology that has clinical applications.