and G540 form H-bond interactions with the 3-keto group of the substrate, while the deprotonated Y363 is positioned in close vicinity (1.9-2.2 Å) to the 2βH atom, prepared to deprotonate the substrate (Figs. ). Y363 forms a direct H-bond interaction with Y118, which seems to be stabilizing its tyrosyl form. The Y363-Y118 tandem is connected via water to four other tyrosines (Y115, Y463, Y466, and Y467) that provide H-bonding interactions for several water molecules (Figure ). These tyrosines, together with water molecules, form a proton relay that enabless the proton's swift transfer from the active site to the solvent. The water molecule connecting the Y363-Y118 tandem with the proton relay system is not only present in the crystal structure (HOH701 in chain A) but its position is also stable during most of the MD simulations.