Leukotriene A4 hydrolase: Analysis of structure–function relationships by site-directed mutagenesis and X-ray crystallography

J.Z. Haeggström, M.J. Mueller, M. Andberg, A. Wetterholm, P. Nordlund, M.M.G.M. Thunnissen

Research output: Contribution to journalArticle in a proceedings journalScientific

Abstract

The leukotrienes are a family of lipid mediators involved in inflammation and allergy. Leukotriene B4 (LTB4) is a classical chemoattractant which triggers adherence and aggregation of leukocytes to the vascular endothelium at only nM concentrations. In addition, leukotriene B4 modulates immune responses, participates in the host defense against infections, and is a key mediator of PAF-induced lethal shock. The final step in the biosynthesis of leukotriene B4 is catalyzed by leukotriene A4 (LTA4) hydrolase, a unique bifunctional zinc metalloenzyme with anion-dependent aminopeptidase activity. This article describes the most recent developments regarding our understanding of the structure, function, and catalytic mechanisms of leukotriene A4 hydrolase, with emphasis on conclusions drawn from mutagenetic analyses and X-ray crystallography.
Original languageEnglish
Pages (from-to)377-387
JournalInternational Congress Series
Volume1233
DOIs
Publication statusPublished - 2002
MoE publication typeB3 Non-refereed article in conference proceedings

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Mutagenesis
Leukotriene B4
X ray crystallography
Allergies
Aminopeptidases
Leukotrienes
Biosynthesis
Chemotactic Factors
Anions
Zinc
Agglomeration
Lipids
leukotriene A4 hydrolase

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Haeggström, J.Z. ; Mueller, M.J. ; Andberg, M. ; Wetterholm, A. ; Nordlund, P. ; Thunnissen, M.M.G.M. / Leukotriene A4 hydrolase: Analysis of structure–function relationships by site-directed mutagenesis and X-ray crystallography. In: International Congress Series. 2002 ; Vol. 1233. pp. 377-387.
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Leukotriene A4 hydrolase: Analysis of structure–function relationships by site-directed mutagenesis and X-ray crystallography. / Haeggström, J.Z.; Mueller, M.J.; Andberg, M.; Wetterholm, A.; Nordlund, P.; Thunnissen, M.M.G.M.

In: International Congress Series, Vol. 1233, 2002, p. 377-387.

Research output: Contribution to journalArticle in a proceedings journalScientific

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AB - The leukotrienes are a family of lipid mediators involved in inflammation and allergy. Leukotriene B4 (LTB4) is a classical chemoattractant which triggers adherence and aggregation of leukocytes to the vascular endothelium at only nM concentrations. In addition, leukotriene B4 modulates immune responses, participates in the host defense against infections, and is a key mediator of PAF-induced lethal shock. The final step in the biosynthesis of leukotriene B4 is catalyzed by leukotriene A4 (LTA4) hydrolase, a unique bifunctional zinc metalloenzyme with anion-dependent aminopeptidase activity. This article describes the most recent developments regarding our understanding of the structure, function, and catalytic mechanisms of leukotriene A4 hydrolase, with emphasis on conclusions drawn from mutagenetic analyses and X-ray crystallography.

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