In most, this site is located in a cavity or a pocket ton the enzyme surface. This frequently has a cleft marking the boundary between two or more major domains. The active site separates substrate molecules from the surrounding solution and places them in environments which have unique characteristics, such as partial exclusion of water. A number of mechanisms operate to contribute to formation of the transition state. One is bringing reacting molecules into close proximity.
Many reactions involve combination or interaction of two or more reactant molecules.
For the reaction to take place, the substrate molecule must collide. The required collisions may be rate among reactant molecules suspended in free solution, particularly if the substrates are present in low concentrations. Binding at the active site of an enzyme brings the reactants close together, raising their effective concentration in the active site to many time the concentration in the surrounding solution. A second contribution mechanism is orienting reactants in positions favoring their interaction. Binding at the active site may bring substrate molecules into an arrangement in which they can collide ate exactly the correct positions and angles required for achievement of the transition state.