InChI=1S/C21H35N8O17P3S/c1- 21(2,16(32) 19(33) 24- 4- 3- 12(30) 23- 5- 6- 50- 28- 34) 8- 43- 49(40,41) 46- 48(38,39) 42- 7- 11- 15(45- 47(35,36) 37) 14(31) 20(44- 11) 29- 10- 27- 13- 17(22) 25- 9- 26- 18(13) 29/h9- 11,14- 16,20,31- 32H,3- 8H2,1- 2H3,(H,23,30) (H,24,33) (H,38,39) (H,40,41) (H2,22,25,26) (H2,35,36,37) /p- 4/t11- ,14- ,15- ,16+,20- /m1/s1 |
CNWRHTNOZSOAKE-IBOSZNHHSA-J |
CC(C) (COP([O- ] ) (=O) OP([O- ] ) (=O) OC[C@H] 1O[C@H] ([C@H] (O) [C@@H] 1OP([O- ] ) ([O- ] ) =O) N1C=NC2=C1N=CN=C2N) [C@@H] (O) C(=O) NCCC(=O) NCCSN=O |
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S-nitroso-CoA
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UniProt
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S-nitroso-coenzyme A tetraanion
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ChEBI
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Stomberski CT, Anand P, Venetos NM, Hausladen A, Zhou HL, Premont RT, Stamler JS (2019) AKR1A1 is a novel mammalian S-nitroso-glutathione reductase. The Journal of biological chemistry 294, 18285-18293 (Source: SUBMITTER) [PubMed:31649033] [show Abstract] Oxidative modification of Cys residues by NO results in S-nitrosylation, a ubiquitous post-translational modification and a primary mediator of redox-based cellular signaling. Steady-state levels of S-nitrosylated proteins are largely determined by denitrosylase enzymes that couple NAD(P)H oxidation with reduction of S-nitrosothiols, including protein and low-molecular-weight (LMW) S-nitrosothiols (S-nitroso-GSH (GSNO) and S-nitroso-CoA (SNO-CoA)). SNO-CoA reductases require NADPH, whereas enzymatic reduction of GSNO can involve either NADH or NADPH. Notably, GSNO reductase (GSNOR, Adh5) accounts for most NADH-dependent GSNOR activity, whereas NADPH-dependent GSNOR activity is largely unaccounted for (CBR1 mediates a minor portion). Here, we de novo purified NADPH-coupled GSNOR activity from mammalian tissues and identified aldo-keto reductase family 1 member A1 (AKR1A1), the archetypal mammalian SNO-CoA reductase, as a primary mediator of NADPH-coupled GSNOR activity in these tissues. Kinetic analyses suggested an AKR1A1 substrate preference of SNO-CoA > GSNO. AKR1A1 deletion from murine tissues dramatically lowered NADPH-dependent GSNOR activity. Conversely, GSNOR-deficient mice had increased AKR1A1 activity, revealing potential cross-talk among GSNO-dependent denitrosylases. Molecular modeling and mutagenesis of AKR1A1 identified Arg-312 as a key residue mediating the specific interaction with GSNO; in contrast, substitution of the SNO-CoA-binding residue Lys-127 minimally affected the GSNO-reducing activity of AKR1A1. Together, these findings indicate that AKR1A1 is a multi-LMW-SNO reductase that can distinguish between and metabolize the two major LMW-SNO signaling molecules GSNO and SNO-CoA, allowing for wide-ranging control of protein S-nitrosylation under both physiological and pathological conditions. |
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