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

M. Andberg, A. Wetterholm, J.F. Medina, J.Z. Haeggström

Research output: Contribution to journalArticleScientificpeer-review

14 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)621-625
JournalBiochemical Journal
Volume345
Issue number3
DOIs
Publication statusPublished - 2000
MoE publication typeA1 Journal article-refereed

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Glutamic Acid
Epoxide Hydrolases
Aminopeptidases
Leukotriene B4
Chemotactic Factors
Metalloproteases
Inhibitory Concentration 50
Enzymes
ubenimex
leukotriene A4 hydrolase
Inhibition (Psychology)

Cite this

Andberg, M. ; Wetterholm, A. ; Medina, J.F. ; Haeggström, J.Z. / Leukotriene A4 hydrolase: A critical role of glutamic acid-296 for the binding of bestatin. In: Biochemical Journal. 2000 ; Vol. 345, No. 3. pp. 621-625.
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abstract = "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.",
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Leukotriene A4 hydrolase: A critical role of glutamic acid-296 for the binding of bestatin. / Andberg, M.; Wetterholm, A.; Medina, J.F.; Haeggström, J.Z.

In: Biochemical Journal, Vol. 345, No. 3, 2000, p. 621-625.

Research output: Contribution to journalArticleScientificpeer-review

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T1 - Leukotriene A4 hydrolase: A critical role of glutamic acid-296 for the binding of bestatin

AU - Andberg, M.

AU - Wetterholm, A.

AU - Medina, J.F.

AU - Haeggström, J.Z.

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AB - 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.

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