Theories of enzyme specificity and their application to proteases and aminoacyl-transfer RNA synthetases.
The question of enzyme specificity which is a corollary of the phenomenon of biological recognition is reviewed. The following theories are outlined briefly: non-productive binding, induced fit, transition state binding, the general strain theory and the kinetic proofreading hypothesis. Data on proteolytic enzymes and aminoacyl-tRNA synthetases are discussed in the light of predictions made by the various theories. The specificity of inhibitor and substrate binding to chymotrypsin and subtilisins is revealed at the sub-molecular level as an example of binding specificity. Kinetic specificity is experimentally distinguished from binding specificity. Conformational adaptability of enzyme and substrate, which is crucial in some theories, is documented by data on aminoacyl-tRNA synthetases. Expected and observed specificity of tRNA charging is discussed with regard to a theoretical limit of specificity. Additional means seem necessary beside those contained in the isolated enzyme-substrate system to account for the high specificity of most synthetases. In conclusion, we have arrived at quite good explanations for moderate specificity such as is displayed by many proteases, but there are still ample difficulties in the understanding of highly specific enzyme reactions.
D000494:Allosteric Regulation; D000604:Amino Acyl-tRNA Synthetases / Q000378:metabolism*; D001665:Binding Sites; D001667:Binding, Competitive; D002384:Catalysis; D007700:Kinetics; D008954:Models, Biological; D010447:Peptide Hydrolases / Q000378:metabolism*; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D010447:Peptide Hydrolases; D000604:Amino Acyl-tRNA Synthetases