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Molecular pharmacology1992; 42(6); 1014-1019;

Cross-species comparison of 5-lipoxygenase-activating protein.

Abstract: To identify regions of 5-lipoxygenase-activating protein (FLAP) important for the function of the protein and the binding of leukotriene biosynthesis inhibitors, we performed a cross-species analysis of FLAP. FLAP from all 10 mammalian species analyzed (human, monkey, horse, pig, cow, sheep, rabbit, dog, rat, and mouse) were immunologically cross-reactive and specifically bound leukotriene biosynthesis inhibitors with high affinity. Using the polymerase chain reaction, cDNA clones for FLAP from six species (monkey, horse, pig, sheep, rabbit, and mouse) were isolated and sequenced. The deduced amino acid sequences of FLAP show a high degree of identity to each other and to the published sequences for human and rat FLAP. Two regions of the protein are almost totally conserved among all of the species analyzed. This suggests that these regions have functional significance and may be involved in inhibitor binding.
Publication Date: 1992-12-01 PubMed ID: 1480129
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  • Comparative Study
  • Journal Article

Summary

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This research paper analyzes the 5-lipoxygenase-activating protein (FLAP) across different mammalian species to pinpoint regions that are important for its function and binding of leukotriene biosynthesis inhibitors.

Research Objective

  • The study aims to identify crucial regions of the 5-lipoxygenase-activating protein (FLAP) that play a significant role in the protein’s function and its ability to bind leukotriene biosynthesis inhibitors.

Methodology

  • FLAP across 10 different mammalian species – human, monkey, horse, pig, cow, sheep, rabbit, dog, rat, and mouse were cross-examined to see if they specifically bind leukotriene biosynthesis inhibitors.
  • Using the polymerase chain reaction technique, cDNA clones for FLAP from six species – monkey, horse, pig, sheep, rabbit, and mouse were isolated and sequenced.

Findings

  • The study findings revealed that FLAP from all ten analyzed species were immunologically cross-reactive, meaning they produce similar immune responses and bound leukotriene biosynthesis inhibitors with high affinity.
  • The sequenced cDNA clones from the six species showed a high degree of identity to each other and also to the already published sequences of human and rat FLAP.
  • Two regions of FLAP protein exhibited almost total conservation across all species, implying these areas might be functionally significant and possibly linked to inhibitor binding.

Importance of the Findings

  • This research is crucial as it explores animal models to identify key aspects of FLAP, providing valuable information about the protein’s function.
  • Understanding these conserved regions could lead to the development of more effective drugs for conditions related to leukotriene biosynthesis, such as inflammation and asthma.

Cite This Article

APA
Vickers PJ, O'Neill GP, Mancini JA, Charleson S, Abramovitz M. (1992). Cross-species comparison of 5-lipoxygenase-activating protein. Mol Pharmacol, 42(6), 1014-1019.

Publication

ISSN: 0026-895X
NlmUniqueID: 0035623
Country: United States
Language: English
Volume: 42
Issue: 6
Pages: 1014-1019

Researcher Affiliations

Vickers, P J
  • Department of Pharmacology, Merck Frosst Centre for Therapeutic Research, Pointe Claire-Dorval, Q, Canada.
O'Neill, G P
    Mancini, J A
      Charleson, S
        Abramovitz, M

          MeSH Terms

          • 5-Lipoxygenase-Activating Proteins
          • Affinity Labels
          • Amino Acid Sequence
          • Animals
          • Base Sequence
          • Carrier Proteins / genetics
          • Carrier Proteins / metabolism
          • Cattle
          • Cross Reactions
          • DNA
          • Dogs
          • Horses
          • Humans
          • Macaca mulatta
          • Membrane Proteins / genetics
          • Membrane Proteins / metabolism
          • Molecular Sequence Data
          • Plasmids
          • Polymerase Chain Reaction
          • Precipitin Tests
          • Rabbits
          • Sequence Homology, Amino Acid
          • Species Specificity
          • Swine

          Citations

          This article has been cited 4 times.
          1. Blevitt JM, Hack MD, Herman K, Chang L, Keith JM, Mirzadegan T, Rao NL, Lebsack AD, Milla ME. A Single Amino Acid Difference between Mouse and Human 5-Lipoxygenase Activating Protein (FLAP) Explains the Speciation and Differential Pharmacology of Novel FLAP Inhibitors. J Biol Chem 2016 Jun 10;291(24):12724-12731.
            doi: 10.1074/jbc.M116.725325pubmed: 27129215google scholar: lookup
          2. Harry GJ, Billingsley M, Bruinink A, Campbell IL, Classen W, Dorman DC, Galli C, Ray D, Smith RA, Tilson HA. In vitro techniques for the assessment of neurotoxicity. Environ Health Perspect 1998 Feb;106 Suppl 1(Suppl 1):131-58.
            doi: 10.1289/ehp.98106s1131pubmed: 9539010google scholar: lookup
          3. Byrum RS, Goulet JL, Griffiths RJ, Koller BH. Role of the 5-lipoxygenase-activating protein (FLAP) in murine acute inflammatory responses. J Exp Med 1997 Mar 17;185(6):1065-75.
            doi: 10.1084/jem.185.6.1065pubmed: 9091580google scholar: lookup
          4. Welsch DJ, Creely DP, Hauser SD, Mathis KJ, Krivi GG, Isakson PC. Molecular cloning and expression of human leukotriene-C4 synthase. Proc Natl Acad Sci U S A 1994 Oct 11;91(21):9745-9.
            doi: 10.1073/pnas.91.21.9745pubmed: 7937884google scholar: lookup