Similarity in shape dictates signature intrinsic dynamics despite no functional conservation in TIM Barrel enzymes

The triosephosphate isomerase barrel fold (TBF), renowned for its 8 β-strand-α-helix repeats that close to form a barrel, is one of the most diverse and abundant folds found in known protein structures. Proteins with this fold have diverse enzymatic functions spanning five of six Enzyme Commission classes. We showed that despite their functional diversity TIM barrel enzymes share signature dynamics. We suggest that the global conservation of the intrinsic dynamics in the TBF contributes greatly to its success as an enzymatic scaffold both through evolution and enzyme design.