Anatomy of a conformational change: hinged "lid" motion of the triosephosphate isomerase loop.
Triosephosphate isomerase (TIM) is used as a model system for the study of how a localized conformational change in a protein structure is produced and related to enzyme reactivity. An 11-residue loop region moves more than 7 angstroms and closes over the active site when substrate binds. The loop acts like a "lid" in that it moves rigidly and is attached by two hinges to the remainder of the protein. The nature of the motion appears to be built into the loop by conserved residues; the hinge regions, in contrast, are not conserved. Results of molecular dynamics calculations confirm the structural analysis and suggest a possible ligand-induced mechanism for loop closure.
Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139.
D
D
Joseph
G A
GA
Petsko
M
M
Karplus
D000595:Amino Acid Sequence; D001665:Binding Sites; D002238:Carbohydrate Epimerases / Q000378:metabolism*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D012984:Software; D014305:Triose-Phosphate Isomerase / Q000378:metabolism*
D002238:Carbohydrate Epimerases; D014305:Triose-Phosphate Isomerase