A structural perspective on enzymes and their catalytic mechanisms

In this perspective, we analyse the progress made in our knowledge of enzyme sequences, structures and functions in the last 2 years. We review how much new enzyme data have been garnered and annotated, derived from the study of proteins using structural and computational approaches. Recent advances towards capturing 'Catalysis in silico' are described, including knowledge and predictions of enzyme structures, their interactions and mechanisms. We highlight the flood of enzyme data, driven by metagenomic sequencing, the improved enzyme data resources, the high coverage in Protein Data Bank of E.C. classes and the AI-driven structure prediction techniques that facilitate the accurate prediction of protein structures. We note the focus on disordered regions in the context of enzyme regulation and specificity and comment on emerging bioinformatic approaches that capture reaction mechanisms computationally for comparing and predicting enzyme mechanisms. We also consider the drivers of progress in this field in the next five years.