TIM barrel
Encyclopedia
The TIM barrel is a conserved
protein fold
consisting of eight α-helices
and eight parallel β-strands
that alternate along the peptide backbone
. The structure is named after triosephosphate isomerase, a conserved glycolytic enzyme
. TIM barrels are quite common among the conserved protein folds. One of the most intriguing features among members of this class of proteins is although they all exhibit the same tertiary fold there is very little sequence homology between them. At least 15 distinct enzyme families use this framework to generate the appropriate active site geometry, always at the C-terminal end of the eight parallel beta-strands of the barrel.
. The parallel β-strands form the inner wall of the doughnut (hence, a β-barrel), whereas the α-helices form the outer wall of the doughnut. Each β-strand connects to the next adjacent strand in the barrel through a long right-handed loop that includes one of the helices, so that the ribbon N-to-C coloring in the top view proceeds in rainbow order around the barrel. The TIM barrel can also be thought of, then, as made up of 8 overlapping, right-handed β-α-β super-secondary structures
.
Although the ribbon diagram shows a hole in the protein's central core, the amino acid
side chain
s are not shown in this representation. The protein's core is actually tightly packed, mostly with bulky hydrophobic amino acid residues although a few glycines are needed to allow wiggle room for the highly constrained center of the 8 approximate repeats to fit together. The packing interactions between the strands and helices are also dominated by hydrophobicity and the branched aliphatic residues valine
, leucine
, and isoleucine
comprise about 40% of the total residues in the β-strands .
, which is one reason this fold is so common : the residues required to maintain the structure and the residues that effect enzymatic
catalysis are for the most part distinct subsets : The linking loops can, in fact, be so long that they contain other protein domains.
Conserved sequence
In biology, conserved sequences are similar or identical sequences that occur within nucleic acid sequences , protein sequences, protein structures or polymeric carbohydrates across species or within different molecules produced by the same organism...
protein fold
Protein folding
Protein folding is the process by which a protein structure assumes its functional shape or conformation. It is the physical process by which a polypeptide folds into its characteristic and functional three-dimensional structure from random coil....
consisting of eight α-helices
Alpha helix
A common motif in the secondary structure of proteins, the alpha helix is a right-handed coiled or spiral conformation, in which every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier...
and eight parallel β-strands
Beta sheet
The β sheet is the second form of regular secondary structure in proteins, only somewhat less common than the alpha helix. Beta sheets consist of beta strands connected laterally by at least two or three backbone hydrogen bonds, forming a generally twisted, pleated sheet...
that alternate along the peptide backbone
Tertiary structure
In biochemistry and molecular biology, the tertiary structure of a protein or any other macromolecule is its three-dimensional structure, as defined by the atomic coordinates.-Relationship to primary structure:...
. The structure is named after triosephosphate isomerase, a conserved glycolytic enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
. TIM barrels are quite common among the conserved protein folds. One of the most intriguing features among members of this class of proteins is although they all exhibit the same tertiary fold there is very little sequence homology between them. At least 15 distinct enzyme families use this framework to generate the appropriate active site geometry, always at the C-terminal end of the eight parallel beta-strands of the barrel.
Structure and composition
TIM barrels are considered α/β protein folds because they include an alternating pattern of α-helices and β-strands in a single domain. In a TIM barrel the helices and strands (usually 8 of each) form a solenoid that curves around to close on itself in a doughnut shape, topologically known as a toroidToroid
Toroid may refer to*Toroid , a doughnut-like solid whose surface is a torus.*Toroidal inductors and transformers which have wire windings on circular ring shaped magnetic cores.*Vortex ring, a toroidal flow in fluid mechanics....
. The parallel β-strands form the inner wall of the doughnut (hence, a β-barrel), whereas the α-helices form the outer wall of the doughnut. Each β-strand connects to the next adjacent strand in the barrel through a long right-handed loop that includes one of the helices, so that the ribbon N-to-C coloring in the top view proceeds in rainbow order around the barrel. The TIM barrel can also be thought of, then, as made up of 8 overlapping, right-handed β-α-β super-secondary structures
.
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
side chain
Side chain
In organic chemistry and biochemistry, a side chain is a chemical group that is attached to a core part of the molecule called "main chain" or backbone. The placeholder R is often used as a generic placeholder for alkyl group side chains in chemical structure diagrams. To indicate other non-carbon...
s are not shown in this representation. The protein's core is actually tightly packed, mostly with bulky hydrophobic amino acid residues although a few glycines are needed to allow wiggle room for the highly constrained center of the 8 approximate repeats to fit together. The packing interactions between the strands and helices are also dominated by hydrophobicity and the branched aliphatic residues valine
Valine
Valine is an α-amino acid with the chemical formula HO2CCHCH2. L-Valine is one of 20 proteinogenic amino acids. Its codons are GUU, GUC, GUA, and GUG. This essential amino acid is classified as nonpolar...
, leucine
Leucine
Leucine is a branched-chain α-amino acid with the chemical formula HO2CCHCH2CH2. Leucine is classified as a hydrophobic amino acid due to its aliphatic isobutyl side chain. It is encoded by six codons and is a major component of the subunits in ferritin, astacin and other 'buffer' proteins...
, and isoleucine
Isoleucine
Isoleucine is an α-amino acid with the chemical formula HO2CCHCHCH2CH3. It is an essential amino acid, which means that humans cannot synthesize it, so it must be ingested. Its codons are AUU, AUC and AUA....
comprise about 40% of the total residues in the β-strands .
Loop regions
Of the approximately 200 residues required to fully form a TIM barrel, about 160 are considered structurally equivalent between different proteins sharing this fold. The remaining residues are located on the loop regions that link the helices and sheets; the loops at the C-terminal end of the sheets tend to contain the active siteActive site
In biology the active site is part of an enzyme where substrates bind and undergo a chemical reaction. The majority of enzymes are proteins but RNA enzymes called ribozymes also exist. The active site of an enzyme is usually found in a cleft or pocket that is lined by amino acid residues that...
, which is one reason this fold is so common : the residues required to maintain the structure and the residues that effect enzymatic
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
catalysis are for the most part distinct subsets : The linking loops can, in fact, be so long that they contain other protein domains.