TIM barrel

The TIM barrel (triose-phosphate isomerase), also known as an alpha/beta barrel,: 252  is a <a href="/facts/Conserved_sequence/YAxy2Xa2">conserved</a> <a href="/facts/Protein_folding/rf3nR2Y1">protein fold</a> consisting of eight <a href="/facts/Alpha_helices/7CESPIYJ">alpha helices</a> (α-helices) and eight parallel <a href="/facts/Beta_strand/B6mwwR6H">beta strands</a> (β-strands) that alternate along the <a href="/facts/Tertiary_structure/VaN6MEYh">peptide backbone</a>. The structure is named after <a href="/facts/Triose-phosphate_isomerase/9dsKLNp0">triose-phosphate isomerase</a>, a conserved metabolic <a href="/facts/Enzyme/DSI1Fh7y">enzyme</a>. TIM barrels are ubiquitous, with approximately 10% of all <a href="/facts/Enzyme/DSI1Fh7y">enzymes</a> adopting this fold. Further, five of seven <a href="/facts/Enzyme_Commission_number/Y5GNLRKX">enzyme commission</a> (EC) enzyme classes include TIM barrel proteins. The TIM barrel fold is <a href="/facts/Conserved_sequence/YAxy2Xa2">evolutionarily ancient</a>, with many of its members possessing little <a href="/facts/Sequence_alignment/p8GQfF7b">similarity</a> today, instead falling within the twilight zone of <a href="/facts/Sequence_similarity/mCIVStrA">sequence similarity</a>.
The inner <a href="/facts/Beta_barrel/8UMBqHQh">beta barrel</a> (β-barrel) is in many cases stabilized by intricate <a href="/facts/Salt_bridge_(protein_and_supramolecular)/cjEeeG9v">salt-bridge networks</a>. <a href="/facts/Turn_(biochemistry)/GdVBHbo3">Loops</a> at the <a href="/facts/C-terminal_end/ws4scHgT">C-terminal ends</a> of the β-barrel are responsible for catalytic activity while <a href="/facts/N-terminal_end/yKYpuaBJ">N-terminal end</a> loops are important for the stability of the TIM-barrels. Structural inserts ranging from extended loops to independent <a href="/facts/Protein_domain/oUpFcSsl">protein domains</a> may be inserted in place of these loops or at the N-terminus/C-terminals. TIM barrels appear to have evolved through <a href="/facts/Gene_duplication/CcfJYsDF">gene duplication</a> and <a href="/facts/Fusion_protein/LCzaDz15">domain fusion</a> events of half-barrel proteins, with a majority of TIM barrels originating from a <a href="/facts/Common_descent/bwEgMu7F">common ancestor</a>. This led many TIM barrels to possess internal symmetries. Further gene duplication events of this ancestral TIM barrel led to diverging enzymes possessing the functional diversity observed today. TIM barrels have also been a longstanding target for <a href="/facts/Protein_design/jFKIHFvc">protein designers</a>. Successful TIM barrel designs include both domain fusions of existing proteins and de novo designs. Domain fusions experiments have resulted in many successful designs, whereas de novo designs only yielded successes after 28 years of incremental development.

TIM barrel open-in-new

TIM barrel