Transition state residual bonding

The catalytic triad consists of the side chains of Asp, His, and Ser close to each other. The Ser residue is reactive and forms a covalent bond with the substrate, thereby providing a specific pathway for the reaction. His has a dual role first, it accepts a proton from Ser to facilitate formation of the covalent bond and, second, it stabilizes the negatively charged transition state. The proton is subsequently transferred to the N atom of the leaving group. Mutations of either of these two residues decrease the catalytic rate by a factor of 10 because they abolish the specific reaction pathway. Asp, by stabilizing the positive charge of His, contributes a rate enhancement of 10. ... 

The active site of an enzyme is generally a pocket or cleft that is specialized to recognize specific substrates and catalyze chemical transformations. It is formed in the three-dimensional structure by a collection of different amino acids (active-site residues) that may or may not be adjacent in the primary sequence. The interactions between the active site and the substrate occur via the same forces that stabilize protein structure hydrophobic interactions, electrostatic interactions (charge-charge), hydrogen bonding, and van der Waals interactions. Enzyme active sites do not simply bind substrates they also provide catalytic groups to facilitate the chemistry and provide specific interactions that stabilize the formation of the transition state for the chemical reaction. 

Figure 10. The ternary complex of the enzyme dihydrofolate reductase, the substrate and the cofactor during the transition state of the hydride ion transfer. The enzyme backbone atoms are shown alone for clarity and are colored blue. The substrate is shown in yellow and the cofactor is in red. The bond colored in light blue indicates the hydride ion being shared by both the cofactor and the substrate before the transfer to the substrate. Water molecules around the residue pteridine of the substrate and the nicotinamide ring of the cofactor alone are shown and colored in light blue. The yellow spheres represent the sodium ions and the pink spheres the chloride ions.

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