Protein: Bifunctional glutathionylspermidine synthetase/amidase (GspSA) [Includes: Glutathionylspermidine amidase (Gsp amidase) (EC 3.5.1.78) (Glutathionylspermidine amidohydrolase [spermidine-forming]); Glutathionylspermidine synthetase (Gsp synthetase) (EC 6.3.1.8) (Glutathione:spermidine ligase [ADP-forming]) (Gsp synthase)] (P0AES0)
Organism: Escherichia coli (strain K12)
Function: Catalyzes the formation of an amide bond between glutathione (GSH) and spermidine coupled with hydrolysis of ATP; also catalyzes the opposing reaction, i.e. the hydrolysis of glutathionylspermidine (Gsp) back to glutathione and spermidine. The amidase active site can also hydrolyze Gsp-disulfide (Gsp-S-S-Gsp) to Gsp-SG and Gsp S-thiolated proteins (GspSSPs) to GSH S-thiolated protein (GSSPs). Likely acts synergistically with glutaredoxin to regulate the redox environment of E.coli and defend against oxidative damage. In vitro, the amidase active site also catalyzes hydrolysis of amide and ester derivatives of glutathione (e.g. glutathione ethyl ester and glutathione amide) but lacks activity toward acetylspermidine (N1 and N8) and acetylspermine (N1).
Sequence: MSKGTTSQDAPFGTLLGYAPGGVAIYSSDYSSLDPQEYEDDAVFRSYIDDEYMGHKWQCVEFARRFLFLNYGVVFTDVGMAWEIFSLRFLREVVNDNILPLQAFPNGSPRAPVAGALLIWDKGGEFKDTGHVAIITQLHGNKVRIAEQNVIHSPLPQGQQWTRELEMVVENGCYTLKDTFDDTTILGWMIQTEDTEYSLPQPEIAGELLKISGARLENKGQFDGKWLDEKDPLQNAYVQANGQVINQDPYHYYTITESAEQELIKATNELHLMYLHATDKVLKDDNLLALFDIPKILWPRLRLSWQRRRHHMITGRMDFCMDERGLKVYEYNADSASCHTEAGLILERWAEQGYKGNGFNPAEGLINELAGAWKHSRARPFVHIMQDKDIEENYHAQFMEQALHQAGFETRILRGLDELGWDAAGQLIDGEGRLVNCVWKTWAWETAFDQIREVSDREFAAVPIRTGHPQNEVRLIDVLLRPEVLVFEPLWTVIPGNKAILPILWSLFPHHRYLLDTDFTVNDELVKTGYAVKPIAGRCGSNIDLVSHHEEVLDKTSGKFAEQKNIYQQLWCLPKVDGKYIQVCTFTVGGNYGGTCLRGDESLVIKKESDIEPLIVVKK
InterPro domains: - IPR016185: Pre-ATP-grasp domain superfamily (homologous_superfamily) [380-510]
- IPR007921: CHAP domain (domain) [34-176]
- IPR051705: Glutathionylspermidine Synthetase/Amidase (family) [6-194]
- IPR038765: Papain-like cysteine peptidase superfamily (homologous_superfamily) [10-197]
- IPR005494: Glutathionylspermidine synthase, pre-ATP-grasp-like domain (domain) [251-615]
Interaction partners: - Polyamine aminopropyltransferase
- Glutathione synthetase
- Glutathione reductase
- Uncharacterized protein YacC
- Glutathione S-transferase YfcF
- Glutathione-specific gamma-glutamylcyclotransferase
- Glutathione hydrolase proenzyme
- Glutathione S-transferase GstB
- Thioredoxin/glutathione peroxidase BtuE
- Glutathione S-transferase GstA
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0003824 (catalytic activity), GO:0016491 (oxidoreductase activity), GO:0016667 (oxidoreductase activity, acting on a sulfur group of donors), GO:0016668 (oxidoreductase activity, acting on a sulfur group of donors, NAD(P) as acceptor), GO:0015036 (disulfide oxidoreductase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0009987 (cellular process), GO:0009058 (biosynthetic process), GO:0044237 (cellular metabolic process), GO:0071704 (organic substance metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0044249 (cellular biosynthetic process), GO:1901576 (organic substance biosynthetic process), GO:1901564 (organonitrogen compound metabolic process), GO:0006790 (sulfur compound metabolic process), GO:1901566 (organonitrogen compound biosynthetic process), GO:0044272 (sulfur compound biosynthetic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005829 (cytosol), GO:0005622 (intracellular anatomical structure), GO:0005737 (cytoplasm)