Sandbox Reserved 1852: Difference between revisions

The key to this enzyme’s success as a catalyst lies in its ability to lower the energy gap between reactants. To accomplish this, the two active site residues, Tyr134 and Glu208, use hydrogen bonding to assist the reaction in a variety of ways. First, it allows specific binding of the ligand in the active site, selecting for molecules with certain geometry at and around the catalytic residues, specifically the carbamate and carbonyl of the diene and dienophile, respectively. This promotes the reaction by lowering the entropy and stabilizing the molecules in close proximity to one another, which also promotes the characteristic stereoselectivity.<ref name="Siegel"/> Second, the bonds affect the energetics of the molecules. By donating a hydrogen to the carbonyl of dienophile, Tyr134 helps to decrease the electron density around the molecule, lowering the energy of the lowest unoccupied molecular orbital (LUMO). Conversely, by abstracting the hydrogen from the carbamate of the dienophile, Glu208 increases the electron density and thus the energy of the highest occupied molecular orbital (HOMO). By closing the gap between these orbitals, the enzyme lowers the activation energy required to allow the orbitals to react. Finally, these interactions help to stabilize the accumulated charges in the transition state. By decreasing electron density in the dienophile, Tyr134 helps to stabilize the accumulated negative charge in the transition state. The Glu208, then, helps stabilize the accumulated positive charge by increasing the electron density of the diene. Calculations predict that this helps to stabilize the transition state by nearly 5 kcal/mol.<ref name="Siegel"/> All together, these interactions make it much easier for the reaction to proceed in a very stereoselective and favorable manner.