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. 2000 Feb 1;345(Pt 3):621–625.

Leukotriene A4 hydrolase: a critical role of glutamic acid-296 for the binding of bestatin.

M Andberg 1, A Wetterholm 1, J F Medina 1, J Z Haeggström 1
PMCID: PMC1220797  PMID: 10642521

Abstract

Leukotriene A(4) hydrolase is a bifunctional Zn(2+)-containing enzyme catalysing the formation of the potent chemotaxin leukotriene B(4). 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 IC(50) 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 A(4) hydrolase; this conclusion might also apply to other members of the M1 family of metallopeptidases.

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Selected References

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