Triosephsophate isomerase is found in nature as a homodimer of approximately 53KDa. TIM is a protein of approximately 250 amino acid residues(4). The tertiary structure of triosephosphate isomerase is an alpha/beta barrel structure. The barrel is formed by an eight fold repeat of an alpha-loop-beta motif.The interior of the barrel is made up of beta sheets. The external surface of the barrel is alpha helices. The active site of TIM is located at the C- terminus of the barrel structure. There are no metal ions or cofactors present in TIM. Three residues along with a flexible loop are involved in the active site. These residues are Lys 12, His 95, and Glu 165. The flexible loop consists of residues 168-174(5). This flexible loop can be found in one of two conformations "open" or "closed." The flexible loop acts as a lid to hold the substrate in the active site and to protect the enediol intermediate from reacting with water during the reaction. Proper closure of the lid is dependent upon formation of a hydrogen bond between tyrosine-208 with alanine-176, a residue of the loop section. These two residues are highly conserved. A mutation of the tyrosine to Phenylanlanine causes a 2000 fold drop in the activity of the enzyme(6). The loop region moves more than 7 angstroms between conformations from opened to closed(7).

Below is an interactive model of triosephosphate isomerase. Push the buttons to view the structure of the molecule. If teh button does not work the first time press again.