TIMbarrellike

TIMbarrellike is a term used in structural biology to describe proteins that adopt a TIM-barrel–like fold, that is, a (β/α)8 barrel topology in which eight beta strands form a barrel surrounded by eight alpha helices. The canonical TIM-barrel fold, named after triose phosphate isomerase, is among the most common enzyme topologies in nature and serves as a versatile scaffold for catalysis.

Structural features: The core is formed by alternating beta strands and alpha helices; the active site commonly lies at the C-terminal end of the beta strands; loop regions connect to form substrate specificity; structural variations include circular permutations and insertions that can preserve the barrel but modify topology.

Functional diversity: TIMbarrellike proteins include many enzymes, such as triosephosphate isomerase, orotidine-5'-phosphate decarboxylase, and various aldolases and dehydratases; some TIMbarrellike proteins function as nonenzymes like binding or regulatory domains; they are distributed across bacteria, archaea, and eukaryotes.

Evolution and engineering: The TIM-barrel framework exhibits notable evolutionary plasticity and is thought to accommodate a wide range of catalytic activities with relatively small sequence changes; this makes TIMbarrellike scaffolds attractive for protein engineering and the design of novel enzymes through loop modification and active-site redesign.

See also: TIM-barrel, protein fold, enzyme catalysis.