Conformational changes observed in enzyme crystal structures upon substrate binding.

The theory of induced fit predicts that enzymes undergo conformational changes as they bind their substrate. We have analysed the structures of 60 different enzymes to see if conformational changes are observed between the apo form, and the substrate (or substrate analog) bound form. In each enzyme the residues responsible for catalysis and substrate binding are known and are examined to see how the active site area is affected by conformational changes. Surprisingly, we find that induced fit motions in most enzymes is very small (usually 1 A RMSD between the apo and substrate-bound forms across the whole protein). We also find that there is a significant difference between the motions undergone by the binding residues and those undergone by the catalytic residues. The binding residues tend to exhibit larger backbone motions, but both binding and catalytic residues show the same, considerable, amount of side-chain flexibility. Knowing the extent of induced fit in enzymes is important for our understanding of the principles of enzyme catalysis and also for improving ligand docking and structural template searching.