Leukotriene A4 hydrolase is a bifunctional Zn2+-containing enzyme catalysing the formation of the potent chemotaxin leukotriene B4. From an analysis of three mutants of Glu-296 we have found that this catalytic residue is critical for the binding of bestatin, a classical aminopeptidase inhibitor. For bestatin, but not for three other tight-binding inhibitors, the IC50 values for inhibition of the epoxide hydrolase activity decreased in the mutants to 0.7-0.003% of the control. Hence Glu-296 is an important structural determinant for binding of bestatin to leukotriene A4 hydrolase; this conclusion might also apply to other members of the M1 family of metallopeptidases.
Andberg, M., Wetterholm, A., Medina, J. F., & Haeggström, J. Z. (2000). Leukotriene A4 hydrolase: A critical role of glutamic acid-296 for the binding of bestatin. Biochemical Journal, 345(3), 621-625. https://doi.org/10.1042/0264-6021:3450621