RGD Reference Report - Molecular and catalytic properties of three rat leukotriene C(4) synthase homologs. - Rat Genome Database

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Molecular and catalytic properties of three rat leukotriene C(4) synthase homologs.

Authors: Schroder, O  Sjostrom, M  Qiu, H  Stein, J  Jakobsson, PJ  Haeggstrom, JZ 
Citation: Schroder O, etal., Biochem Biophys Res Commun. 2003 Dec 12;312(2):271-6.
RGD ID: 2302289
Pubmed: PMID:14637132   (View Abstract at PubMed)

The committed step in the biosynthesis of cysteinyl-leukotrienes is catalyzed by leukotriene C(4) synthase as well as microsomal glutathione S-transferase (MGST) type 2 and type 3, which belong to a family of membrane-associated proteins in eicosanoid and glutathione metabolism (MAPEG). We cloned and characterized these three enzymes from the rat to allow a side-by-side comparison of structural and catalytic properties. The proteins are 79.6-86.7% identical to the human orthologs. Rat MGST3 fails to convert leukotriene A(4) into leukotriene C(4), which in turn challenges the proposed catalytic role of a conserved Arg and Tyr residue for the leukotriene C(4) synthase reaction. Comparative inhibitor studies of all three enzymes, using MK-886 and cysteinyl-leukotrienes, indicate that their catalytic centers originate from structurally related and overlapping active sites. Hence, it seems feasible to design enzyme inhibitors, which simultaneously target several members of this protein family to yield compounds with increased anti-inflammatory action.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ltc4sRatleukotriene biosynthetic process  IDA  RGD 

Molecular Function

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Mgst2Ratglutathione peroxidase activity  IDA  RGD 
Mgst3Ratglutathione peroxidase activity  IDA  RGD 
Mgst2Ratglutathione transferase activity  IDA  RGD 
Mgst2Ratleukotriene-C4 synthase activity  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ltc4s  (leukotriene C4 synthase)
Mgst2  (microsomal glutathione S-transferase 2)
Mgst3  (microsomal glutathione S-transferase 3)

Additional Information