Alternative titles; symbols
HGNC Approved Gene Symbol: MGST2
Cytogenetic location: 4q31.1 Genomic coordinates (GRCh38): 4:139,665,819-139,754,618 (from NCBI)
Glutathione S-transferases (GSTs), such as MGST2, are products of a gene superfamily that catalyze the conjugation of glutathione with a variety of xenobiotics and their reactive metabolites (Jakobsson et al., 1996).
Two proteins involved in leukotriene biosynthesis are 5-lipoxygenase-activating protein (FLAP; 603700) and leukotriene (LT) C4 synthase (LTC4S; 246530); these proteins are 31% identical at the amino acid level. Jakobsson et al. (1996) identified a novel human gene in the FLAP/LTC4 synthase gene family which they termed microsomal glutathione S-transferase II (microsomal GST-II). This gene encodes a 147-amino acid polypeptide which is 44% identical to LTC4 synthase, 33% identical to FLAP, and 11% identical to human microsomal GST1 (138330). Northern blot analysis found that the gene is expressed as a 0.6-kb transcript in a variety of human tissues, but only weakly expressed (if at all) in lung, brain, placenta, and bone marrow. In contrast, FLAP mRNA is expressed in lung, various organs of the immune system, and peripheral blood leukocytes.
Sjostrom et al. (2001) found that MGST2 was the only GST expressed in human umbilical vein endothelial cells (HUVECs). Northern blot analysis of HUVECs detected major and minor mRNAs at about 0.7 and 0.6 kb, respectively. Western blot analysis of HUVEC lysate detected MGST2 at an apparent molecular mass of about 16 kD.
Jakobsson et al. (1996) showed that the enzyme encoded by the GST2 gene is associated with cell microsomes and can catalyze the production of LTC4 from LTA4 and reduced glutathione.
Sjostrom et al. (2001) found that MGST2 accepted both the free acid and the methyl ester of LTA4 as substrate, but the free acid was the preferred substrate. MGST2 was susceptible to dose-dependent inhibition by its product, LTC4. The gamma-glutamyl-cysteinyl-glycyl moiety of LTC4 was important for inhibition of MGST2, presumably via interaction with a GSH-binding pocket.
Jakobsson et al. (1996) localized the MGST2 gene to human chromosome 4q28-q31 by fluorescence in situ hybridization.
Jakobsson, P.-J., Mancini, J. A., Ford-Hutchinson, A. W. Identification and characterization of a novel human microsomal glutathione S-transferase with leukotriene C4 synthase activity and significant sequence identity to 5-lipoxygenase-activating protein and leukotriene C4 synthase. J. Biol. Chem. 271: 22203-22210, 1996. [PubMed: 8703034] [Full Text: https://doi.org/10.1074/jbc.271.36.22203]
Sjostrom, M., Jakobsson, P.-J., Heimburger, M., Palmblad, J., Haeggstrom, J. Z. Human umbilical vein endothelial cells generate leukotriene C4 via microsomal glutathione S-transferase type 2 and express the CysLT1 receptor. Europ. J. Biochem. 268: 2578-2586, 2001. [PubMed: 11322876] [Full Text: https://doi.org/10.1046/j.1432-1327.2001.02142.x]