TIMBarrel

TIMbarrel, also known as the TIM-barrel fold, refers to a common protein architectural motif in which eight beta-strands form a central barrel that is surrounded by eight alpha-helices in a (β/α)8 arrangement. The fold is named after triosephosphate isomerase (TIM), an enzyme in glycolysis that exemplifies this structure. In the canonical TIMbarrel, the beta-strands create a core barrel while the alpha-helices pack on the exterior, and the active site typically lies near the C-terminal ends of the beta-strands. The catalytic residues are often provided by the loops connecting beta strands to adjacent helices, giving the fold remarkable versatility for chemical transformations.

TIMbarrel enzymes are among the most chemically diverse in biology, capable of supporting a broad range of reactions, including isomerization, decarboxylation, and lyase activities. This architectural flexibility, combined with a robust and modular scaffold, has made the TIMbarrel fold a frequent subject of study in structural biology and protein engineering. The fold is widely distributed across bacteria, archaea, and eukaryotes, and its conservation across distant families suggests an ancient origin with enduring utility.

Notable members of the TIMbarrel superfamily include triosephosphate isomerase, orotidine 5'-phosphate decarboxylase, and ketosteroid isomerase, among others. Because of its stability and adaptable active-site loops, the TIMbarrel scaffold is commonly used in protein design and directed evolution to create enzymes with novel or improved functions.