E:S si E:S 0.0 0.0 0.0 0.0 E:S Strans. Finally, we have also analyzed the same process for the apoenzyme, without substrates or product present in the active site. Such a model represents the situation when water molecules can penetrate the active site despite its hydrophobicity, and the geometry of the enzyme is not influenced by the strong binding of fumarate. Besides the presence of three Furthermore, to reach the si face of the glycyl radical, Cys493 has to attain a higher energy conformation for pushing away the hydrophobic residues of Leu391 and Val709.