Highlight talk – Theme: Proteins
Abstract
How enzymes, as biological catalysts, evolved their functions remains a fundamental question in biology. Using sophisticated tools relating sequences and structures across thousands of genomes though phylogenetic analysis and novel measures of functional similarity we have compiled information on all experimentally annotated changes in enzyme function within 379 structurally defined protein domain superfamilies, linking the changes observed in functions during evolution to changes in reaction chemistry. Using analysis of modifications in reaction chemistry and enzymes active sites we have observed that some superfamilies have changed the reactions they perform without changing catalytic machinery. In others large changes of enzyme function have been brought about by significant changes in catalytic machinery. Interestingly, in some superfamilies relatives perform similar functions but with different catalytic machineries. This provides elemental insights for predicting the function of uncharacterised sequences, the design of new synthetic enzymes as well as the application to the development of therapeutics.
Authors
Nicholas Furnham, London School of Hygiene and Tropical Medicine, United Kingdom
Natalie Dawson, University College London, United Kingdom
Syed Rahman, European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), United Kingdom
Janet M. Thornton, EMBL- European Bioinformatics Institute (EBI), United Kingdom
Christine Orengo, University College London, United Kingdom
Source of publication
2016, Journal of Molecular Biology, Vol 428, pp 253-67