Ancestral Enzymes

 
 

Superposition of crystal structures for all 10 Class I aminoacyl-tRNA synthetases onto the structures of the B. stearothermophilus TrpRS allowed us to identify a 130 residue, disjoint subset containing the intact active site. When we constructed and expressed this "minimal catalytic domain" we found it had 65% of the transition state stabilization free energy of the intact dimeric enzyme. We called this construct an "Urzyme" from Ur, the German prefix meaning "primitive, original" plus enzyme.


The five superpositions shown here suggest that there are Urzymes of 60-130 residues in all five diverse enzyme superfamilies. We have characterized those for the Class I and Class II aminoacyl-tRNA synthetases and have begun working on a deaminase Urzyme.


We have now shown that the observed catalytic activity for both TrpRS and HisRS Urzymes is authentic. Urzymes therefore demonstrate that the most highly conserved sequences and secondary structures in these enzyme superfamilies also retain considerable enzymatic activity and specificity. They are thus valid models for the earliest ancestral enzymes. See more details

 

Urzymology:  identifying and characterizing the earliest protein catalysts

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