Analogous enzymes: independent inventions in enzyme evolution

Area of Science:

• Biochemistry
• Enzymology
• Evolutionary Biology

Background:

• The same biochemical reaction can be catalyzed by enzymes with different protein structures.
• Homologous enzymes share evolutionary origins, while analogous enzymes do not necessarily.

Purpose of the Study:

• To systematically search for analogous enzymes across different enzyme classes.
• To investigate the evolutionary origins and distribution of analogous enzymes.
• To explore the potential of analogous enzymes as drug targets.

Main Methods:

• Systematic search for analogous enzymes using sequence conservation analysis.
• Evaluation of enzymes sharing the same Enzyme Commission (EC) number.
• Utilizing sensitive, iterative sequence database search methods.
• Structural fold comparison to confirm independent evolutionary origins.

Main Results:

• Identified analogous enzymes for 105 EC numbers, involving 243 distinct proteins.
• Confirmed independent evolutionary origins for 34 cases by distinct structural folds.
• Found analogous enzymes across all enzyme classes, with patchy distribution in biochemical pathways.
• Observed differences between bacterial and eukaryotic forms of analogous enzymes.

Conclusions:

• Convergent evolution is a significant factor in enzyme evolution, leading to analogous enzymes.
• The patchy distribution suggests gene transfer and selective loss events shaped enzyme repertoires.
• Recruitment of enzymes with similar but distinct functions is a key evolutionary scenario.
• Bacterial and eukaryotic analogous enzymes represent potential targets for novel antibacterial drug development.