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Studies on the Active Site of Leukotriene A4 Hydrolase

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Eicosanoids and other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury 3

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 407))

Abstract

Leukotriene (LT) A4 hydrolase (EC 3.3.2.6) is a soluble monomeric protein with a molecular mass of 69 kDa that converts the unstable epoxide intermediate LTA4 into the proinflammatory compound LTB4, 5(S), 12(R)-dihydroxy-6, 14-cis-8, 10-trans-eicosa-tetraenoic acid (For reviews see Refs. 1 and 2). Sequence comparisons of LTA4 hydrolase with certain zinc containing proteases and peptidases led to the discovery of a zinc binding motif in the primary structure of the enzyme3. Further studies verified that LTA4 hydrolase indeed contained one zinc atom per enzyme molecule4,5. These findings also led to the discovery of a previously unknown peptidase/amidase activity5,6 which was specifically stimulated by monovalent anions, e. g., chloride ions7, and also by albumin8. Studies involving site directed mutagenesis in combination with metal determination of the purified mutated proteins demonstrated that the zinc atom was bound to His-295, His-299, and Glu-318, in accordance with previous predictions, and that replacements of either of these three residues led to enzymatically inactive proteins which did not contain zinc9.

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Authors and Affiliations

  1. Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77, Stockholm, Sweden

    Anders Wetterholm, Martin J. Mueller, Martina Blomster, Bengt Samuelsson & Jesper Z. Haeggström

Authors
  1. Anders Wetterholm
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  2. Martin J. Mueller
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  3. Martina Blomster
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  4. Bengt Samuelsson
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  5. Jesper Z. Haeggström
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Editor information

Editors and Affiliations

  1. Wayne State University, Detroit, Michigan, USA

    Kenneth V. Honn

  2. Vanderbilt University, Nashville, Tennessee, USA

    Lawrence J. Marnett

  3. Free University Berlin, Berlin, Germany

    Santosh Nigam

  4. The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China

    Robert L. Jones

  5. University of Medicine and Dentistry of New Jersey, Stratford, New Jersey, USA

    Patrick Y.-K. Wong

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© 1997 Springer Science+Business Media New York

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Wetterholm, A., Mueller, M.J., Blomster, M., Samuelsson, B., Haeggström, J.Z. (1997). Studies on the Active Site of Leukotriene A4 Hydrolase. In: Honn, K.V., Marnett, L.J., Nigam, S., Jones, R.L., Wong, P.YK. (eds) Eicosanoids and other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury 3. Advances in Experimental Medicine and Biology, vol 407. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1813-0_1

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  • DOI: https://doi.org/10.1007/978-1-4899-1813-0_1

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4899-1815-4

  • Online ISBN: 978-1-4899-1813-0

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