Alternative titles; symbols
HGNC Approved Gene Symbol: MPST
Cytogenetic location: 22q12.3 Genomic coordinates (GRCh38): 22:37,019,742-37,029,815 (from NCBI)
Mercaptopyruvate sulfurtransferase (EC 2.8.1.2) catalyzes the transfer of a sulfur atom from mercaptopyruvate to sulfur acceptors like cyanides or thiol compounds. MPST plays a central role in both cysteine degradation and cyanide detoxification (summary by Billaut-Laden et al., 2006).
By screening a human adult liver cDNA expression library with polyclonal antibodies against bovine liver rhodanese (180370), Pallini et al. (1991) isolated a cDNA, which they thought was rhodanese (TST; 180370), but which was later said by Aita et al. (1997) to encode mercaptopyruvate sulfurtransferase (MPST). The MPST cDNA identified by Pallini et al. (1991) encodes a predicted 295-amino acid protein that is 57% identical to bovine rhodanese. Northern blot analysis identified a 1.4-kb MPST transcript in adult liver. Aita et al. (1997) stated that MPST and rhodanese share 60% amino acid sequence identity.
By characterizing the rat enzymes, Nagahara et al. (1995) found that cytosolic Mst is evolutionarily related to mitochondrial rhodanese. Their active-site regions are similar, with identical catalytic cys246 and arg185 residues, and both catalyze sulfurtransferase reactions. Point mutation studies showed that the specificities of their reactions were determined by other active-site residues: arg247 and lys248 in rhodanese, and gly247 and ser248 in Mst.
Nagahara et al. (2004) determined that the MPST gene contains 2 exons. It has properties of a housekeeping gene, including a promoter region with prominent GC-rich sequences with many CpG and GpC dinucleotides, and a GC box rather than a TATA box. MPST has 4 possible transcriptional start sites. The intron contains a complementary xenobiotic responsive element. Point mutagenesis and deletion studies revealed a silencer element localized around -390C and an enhancer element around -377G.
Hartz (2009) mapped the MPST gene to chromosome 22q12.3 based on an alignment of the MPST sequence (GenBank B1597227) with the genomic sequence (GRCh37). The TST gene also maps to 22q12.3.
Aita, N., Ishii, K., Akamatsu, Y., Ogasawara, Y., Tanabe, S. Cloning and expression of human liver rhodanese cDNA. Biochem. Biophys. Res. Commun. 231: 56-60, 1997. [PubMed: 9070219] [Full Text: https://doi.org/10.1006/bbrc.1996.6046]
Billaut-Laden, I., Rat, E., Allorge, D., Crunelle-Thibaut, A., Cauffiez, C., Chevalier, D., Lo-Guidice, J.-M., Broly, F. Evidence for a functional genetic polymorphism of the human mercaptopyruvate sulfurtransferase (MPST), a cyanide detoxification enzyme. Toxicol. Lett. 165: 101-111, 2006. [PubMed: 16545926] [Full Text: https://doi.org/10.1016/j.toxlet.2006.02.002]
Hartz, P. A. Personal Communication. Baltimore, Md. 12/8/2009.
Nagahara, N., Okazaki, T., Nishino, T. Cytosolic mercaptopyruvate sulfurtransferase is evolutionarily related to mitochondrial rhodanese: striking similarity in active site amino acid sequence and the increase in the mercaptopyruvate sulfurtransferase activity of rhodanese by site-directed mutagenesis. J. Biol. Chem. 270: 16230-16235, 1995. [PubMed: 7608189] [Full Text: https://doi.org/10.1074/jbc.270.27.16230]
Nagahara, N., Sreeja, V. G., Li, Q., Shimizu, T., Tsuchiya, T., Fujii-Kuriyama, Y. A point mutation in a silencer module reduces the promoter activity for the human mercaptopyruvate sulfurtransferase. Biochim. Biophys. Acta 1680: 176-184, 2004. [PubMed: 15507321] [Full Text: https://doi.org/10.1016/j.bbaexp.2004.09.007]
Pallini, R., Guazzi, G. C., Cannella, C., Cacace, M. G. Cloning and sequence analysis of the human liver rhodanese: comparison with the bovine and chicken enzymes. Biochem. Biophys. Res. Commun. 180: 887-893, 1991. [PubMed: 1953758] [Full Text: https://doi.org/10.1016/s0006-291x(05)81148-9]