L-LTA4 systems. In L-LTA4 systems, the binding mode of LTA4 in WT system has formed hydrogen bonds with Y383 through the oxygen atom of epoxy ring and the distance between this oxygen atom and the metal ion was maintained in a closer distance compared to that of mutant systems. The carboxylate group of LTA4 in WT system was well recognized by both the positively charged residues R563 and K565 which are reported to be the carboxylate recognition sites. Because of this recognition the carboxylate group has formed strong hydrogen bond interactions with R563 and K565. The distance between the carboxylate of E271 and metal (Zn 2+ ) ion was maintained in close vicinity for the reported acid-induced catalytic reaction. The other residue Y378 has also formed a hydrogen bond interaction with the carboxylate group of LTA4 ( Figure 7A ). In E271Q system, the binding mode of LTA4 is so different from that of WT system. Because of the uncharged nature of the mutation (E271Q) the metal ion has slightly moved towards the carboxylate group of LTA4, which has also mutually moved towards the metal ion. This movement of carboxylate group of LTA4 has moved the central epoxy group of LTA4 further down and made it inaccessible by the catalytic metal ion ( Figure 7B ). This change in the E271 and distance between Zn 2+ and epoxy group (0.69 nm) can be directly correlated with the loss of activity ( Figure 5A ). The hydrogen bonds formed with R563 and K565 residues were completely lost because of this mutation. In R563A system, though E271 residue has maintained its hold on the metal ion because of the absence of R563, the important carboxylate recognition site, the LTA4 has moved backwards into the hydrophobic cavity formed by hydrophobic residues such as W311, F362, K364, L365, V366, V367, and V381 ( Figure 7C ). This change has not only brought the distance between Zn 2+ and the epoxy ring of LTA4 higher (0.78 nm) compared to any other L-LTA4 systems but also made hydrogen bonding with K565 impossible. In terms of K565A system, the binding mode of LTA4 was similar to that of WT system. Regardless of mutated K565 the hydrogen bonds were maintained with R563 but still the distance between Zn 2+ and epoxy ring of LTA4 was higher (0.68 nm) in this mutant system as well. The hydrogen bond between LTA4 and Y378 was also maintained as observed in WT system ( Figure 7D ). This observation also correlated the experimental observation that K565A mutation reduces the activity but does not abolish it.