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May 13-14, 2019 | Prague, Czech Republic
Chemistry and Medicinal Chemistry
9th World Congress on
Asian Journal of Biomedical and Pharmaceutical Sciences | Volume 9 ISSN: 2249-622X
H2S producing enzyme, 3-mercaptopyruvate sulfurtransferase
Noriyuki Nagahara
Nippon Medical School, Japan
3-Mercaptopyruvate sulfurtransferase (MST, EC
2.8.1.2) is a cystine-catabolizing enzyme involved in the
mercaptopyruvate pathway and evolutionarily related to
mitochondrial rhodanese (TST, EC 2.8.1.1). MST is a 33 kDa
simple protein enzyme, which catalyzes transsulfuration
reaction. An active site Cys 247 is the site of persulfide
formation during catalysis (Nagahara et al., J Biol Chem,
2005, Nagahara & Sawada, 2006, Nagahara et al., J
Biol Chem, 2007). MST is found in all the tissues in rat
and mouse; however, its activity differs in each tissue.
Subcellular fractionation analysis revealed that eukaryotic
MST activity was observed in both the cytoplasm and
mitochondria (Nagahara et al., Histochem. Cell Biol,
1998, Tomita et al., Molecules, 2016). Interestingly, it is
distributed in both prokaryotes and eukaryotes. MST has
been demonstrated to serve multiple roles (Nagahara et
al., Methods Enzymol, 2015, Nagahara, Bri J Pharmacol,
2018) as H 2 S and polysulfide production (Ida et al ., Proc Natl
Acad Sci USA, 2014, Kimura et al ., Sci Rep, 2015, Mikami et
al., Biochem J, 2011, Shibuya et al., Antioxid Redox Signal,
2008, Yadav et al., J Biol Chem, 2013, Nagahara et al.,
Biochem Biophys Res Commun, 2018), antioxidant action
(Nagahara and Katayama, J Biol Chem, 2005, Nagahara et
al., J Biol Chem, 2007), possible SOx production (Nagahara
et al ., Antioxid Redox Signal, 2012), and possible anxiolytic-
like effect (Nagahara et al. Sci Rep, 2013).
It has been reported that hydrogen sulfide and polysulfides
were produced by cystathionine β-synthase (EC 4.2.1.22)
(Abe and Kimura, J Neurosci, 1996), cystathionine γ-lyase
(EC 4.4.1.1) (Hosoki et al., Biochem Biophys Res Commun,
1997), TST (Kimura et al., Sci Rep, 2015; Mikami et al., J
Biol Chem, 2011) and MST. As to antioxidative function,
MST activity is regulated by thioredoxin-dependent redox-
sensing molecular switches; one switch is a catalytic site
cysteine forming a low redox potential sulfenate under
oxidized conditions which is reversibly converted to an
inactive form MST. The other one is exposed cysteines
outside enzyme forming a disulfide between MSTs under
oxidized conditions to be inactive dimeric form. We are
now investigating physiological role of MST using MST-
knockout (KO) and double TST and MST-KO mice. Recently,
we further reported H 2S and polysulfide production
by MST in vitro (Nagahara et al ., Biochem Biophys Res
Commun, 2018).
Speaker Biography
Noriyuki Nagahara, MD., PhD., Biochemistry and Pathological
Chemistry, is associate professor of Nippon Medical School. He makes
a special study of medical biochemistry, molecular biology and organic
chemistry, especially reaction mechanism and enzyme kinetic study on
a transsulfuration enzyme, mercaptopyruvate sulfurtransferase (MST).
He first purified rat MST to homogeneity and succeeded cloning. He
found MST was evolutionarily related to mitochondrial rhodanese via
substitution of amino acids in the active site by genetic engineering
techniques. He certified that MST was an antioxidant enzyme. Recently,
he produced MST-knockout mouse to clarify physiological roles of MST
and a pathogenesis of congenital metabolic disease caused by deficiency
of MST, mercaptolactate-cysteine disulfiduria.
e:
Noriyuki Nagahara, Asian J Biomed Pharmaceut Sci, Volume:9
DOI: 10.4066/2249-622X-C2-020
Notes: