The role of mobility in the substrate binding and catalytic machinery of enzymes.
Recent theoretical and experimental studies have demonstrated that proteins are fluctuating systems capable of large, seemingly random, excursions from the equilibrium conformation. Attention is now focusing on the functional consequences of these motions. X-ray diffraction is a powerful tool for mapping the spatial distribution of protein dynamics; studies on the temperature dependence of the apparent Debye-Waller factors of crystalline myoglobin demonstrate that proteins are flexible in the solid state. Crystallographic studies of a Michaelis complex of ribonuclease A show that a mobile lysine adapts its conformation to the changes in stereochemistry and charge distribution in the substrate during catalysis. The structure of the triose phosphate isomerase-substrate complex shows that a mobile region of 10 amino acids becomes ordered when ligand binds. These studies suggest several roles for protein mobility in enzymic catalysis: providing access to internal sites, allowing changes in substrate structure during the reaction, and reducing the observed binding constant of substrate and product to the enzyme by decreasing entropy. A flexible enzyme also does not need a communication system to signal binding or transformation, since a pre-existing equilibrium can be used. More speculative ideas, such as the guiding of thermal vibrations along the reaction coordinate, can only be tested when more detailed data are available.
D001665:Binding Sites; D004722:Endoribonucleases; D004798:Enzymes / Q000378:metabolism*; D007700:Kinetics; D008024:Ligands; D008954:Models, Biological; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D012259:Ribonuclease, Pancreatic
D004798:Enzymes; D008024:Ligands; D004722:Endoribonucleases; D012259:Ribonuclease, Pancreatic