+1 (202) 780-3397H2S producing enzyme, 3-mercaptopyruvate sulfurtransferase
9th World Congress on Chemistry and Medicinal Chemistry
May 13-14, 2019 | Prague, Czech Republic
Noriyuki Nagahara
Nippon Medical School, Japan
Scientific Tracks Abstracts : Asian J Biomed Pharmaceut Sci
Abstract:
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 Cys247 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 H2S 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 anxiolyticlike 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 redoxsensing 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 MSTknockout (KO) and double TST and MST-KO mice. Recently, we further reported H2S and polysulfide production by MST in vitro (Nagahara et al., Biochem Biophys Res Commun, 2018).
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-mail: noriyuki@nms.ac.jp
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