print visible entries

print all entries

Ligand glutathionylspermidine

Basic Ligand Information

Molecular Structure

Show all BRENDA pathways known for glutathionylspermidine

close all tables

open all tables

Roles as Enzyme Ligand

In Vivo Substrate in Enzyme-catalyzed Reactions (7 results)

top print hide

Show Natural Substrate (7 entries)

EC NUMBER

PROVEN IN VIVO REACTION

REACTION DIAGRAM

LITERATURE

ENZYME 3D STRUCTURE

3.5.1.78

glutathionylspermidine + H2O = glutathione + spermidine

31903, 716863, 727554, 727627

3a2y, 3D-view

3.5.1.78

glutathionylspermidine + H2O = glutathione + spermidine

31903, 716863, 727554, 727627

3o98, 3D-view

3.5.1.78

2 entries

4.4.1.5

glutathionylspermidine + methylglyoxal = ?

692049

-

6.3.1.9

glutathione + glutathionylspermidine + ATP = N1,N8-bis(glutathionyl)spermidine + ADP + phosphate

744910, 662446, 746173, 744964, 746270, 661810, 662802, 661011

-

6.3.1.9

gamma-L-Glu-L-Cys-Gly + N1-(gamma-Glu-L-Cys-Gly)-spermidine + ATP = N1,N8-bis-(gamma-L-glutamyl-L-cysteinyl-glycyl)-spermidine + ADP + phosphate

965, 964

-

6.3.1.9

gamma-L-glutamyl-L-cysteinyl-glycine + N1-(gamma-L-glutamyl-L-cysteinyl-glycyl)-spermidine + ATP = N1,N8-bis-(gamma-L-glutamyl-L-cysteinyl-glycyl)-spermidine + ADP + phosphate

650657, 652306

-

6.3.1.9

N1-glutathionylspermidine + glutathione + ATP = N1,N8-bis(glutathionyl)spermidine + ADP + phosphate

727951, 728592

-

6.3.1.9

4 entries

In Vivo Product in Enzyme-catalyzed Reactions (4 results)

top print hide

Show Natural Product (4 entries)

EC NUMBER

PROVEN IN VIVO REACTION

REACTION DIAGRAM

LITERATURE

ENZYME 3D STRUCTURE

6.3.1.8

glutathione + spermidine + ATP = glutathionylspermidine + ADP + phosphate

-

3a2y, 3D-view

6.3.1.8

glutathione + spermidine + ATP = glutathionylspermidine + ADP + phosphate

-

3o98, 3D-view

6.3.1.9

glutathione + spermidine + ATP = glutathionylspermidine + ADP + phosphate

-

-

6.3.1.9

glutathione + spermidine + ATP = N1-glutathionylspermidine + N8-glutathionylspermidine + ADP + phosphate

-

-

6.3.1.8

2 entries

6.3.1.9

2 entries

Substrate in Enzyme-catalyzed Reactions (13 results)

top print hide

Show Substrate (13 entries)

EC NUMBER

REACTION

REACTION DIAGRAM

LITERATURE

ENZYME 3D STRUCTURE

3.5.1.78

glutathionylspermidine + H2O = glutathione + spermidine

967, 968, 969, 31903, 649733, 712459, 716863, 727554, 727627

3a2y, 3D-view

3.5.1.78

glutathionylspermidine + H2O = glutathione + spermidine

967, 968, 969, 31903, 649733, 712459, 716863, 727554, 727627

3o98, 3D-view

4.4.1.5

glutathionylspermidine + methylglyoxal = ?

692049, 678043

-

4.4.1.5

glutathionylspermidine + phenylglyoxal = ?

678043

-

4.4.1.5

N1-glutathionylspermidine + methylglyoxal = ?

681984

-

6.3.1.8

glutathionylspermidine + H2O = glutathione + spermidine

649733

3a2y, 3D-view

6.3.1.8

glutathionylspermidine + H2O = glutathione + spermidine

649733

3o98, 3D-view

6.3.1.9

glutathione + glutathionylspermidine + ATP = N1,N8-bis(glutathionyl)spermidine + ADP + phosphate

744910, 662446, 746173, 744964, 746270, 661810, 662802, 661011

-

6.3.1.9

gamma-L-Glu-L-alpha-aminobutyrylglycine + N1-(gamma-Glu-L-Cys-Gly)-spermidine + ATP = ?

964

-

6.3.1.9

gamma-L-Glu-L-Cys-Gly + N1-(gamma-Glu-L-Cys-Gly)-spermidine + ATP + H2O = N1,N8-bis-(gamma-L-Glu-L-Cys-Gly)-spermidine + ADP + phosphate + NH3

963, 964, 971

-

6.3.1.9

gamma-L-Glu-L-Cys-Gly + N1-(gamma-Glu-L-Cys-Gly)-spermidine + ATP = N1,N8-bis-(gamma-L-glutamyl-L-cysteinyl-glycyl)-spermidine + ADP + phosphate

965, 964

-

6.3.1.9

gamma-L-glutamyl-L-cysteinyl-glycine + N1-(gamma-L-glutamyl-L-cysteinyl-glycyl)-spermidine + ATP = N1,N8-bis-(gamma-L-glutamyl-L-cysteinyl-glycyl)-spermidine + ADP + phosphate

650657, 652306

-

6.3.1.9

N1-glutathionylspermidine + glutathione + ATP = N1,N8-bis(glutathionyl)spermidine + ADP + phosphate

727951, 728592

-

3.5.1.78

2 entries

4.4.1.5

3 entries

6.3.1.8

2 entries

6.3.1.9

6 entries

Product in Enzyme-catalyzed Reactions (10 results)

top print hide

Show Product (10 entries)

EC NUMBER

REACTION

REACTION DIAGRAM

LITERATURE

ENZYME 3D STRUCTURE

3.5.1.78

trypanothione + H2O = glutathione + glutathionylspermidine

, 649733

3a2y, 3D-view

3.5.1.78

trypanothione + H2O = glutathione + glutathionylspermidine

, 649733

3o98, 3D-view

6.3.1.8

glutathione + spermidine + ATP = glutathionylspermidine + ADP + phosphate

-

3a2y, 3D-view

6.3.1.8

glutathione + spermidine + ATP = glutathionylspermidine + ADP + phosphate

-

3o98, 3D-view

6.3.1.8

gamma-L-Glu-L-Cys-Gly + spermidine + ATP = N1-(gamma-L-Glu-L-Cys-Gly)-spermidine + ADP + phosphate

962, 967, 968, 963, 964, 965, 966

3a2y, 3D-view

6.3.1.8

gamma-L-Glu-L-Cys-Gly + spermidine + ATP = N1-(gamma-L-Glu-L-Cys-Gly)-spermidine + ADP + phosphate

962, 967, 968, 963, 964, 965, 966

3o98, 3D-view

6.3.1.8

gamma-L-Glu-L-Cys-Gly + spermidine + MgATP2- = N1-(gamma-L-Glu-L-Cys-Gly)-spermidine + MgADP- + phosphate

965, 649733, 650561

3a2y, 3D-view

6.3.1.8

gamma-L-Glu-L-Cys-Gly + spermidine + MgATP2- = N1-(gamma-L-Glu-L-Cys-Gly)-spermidine + MgADP- + phosphate

965, 649733, 650561

3o98, 3D-view

6.3.1.9

glutathione + spermidine + ATP = glutathionylspermidine + ADP + phosphate

-

-

6.3.1.9

glutathione + spermidine + ATP = N1-glutathionylspermidine + N8-glutathionylspermidine + ADP + phosphate

-

-

3.5.1.78

2 entries

6.3.1.8

6 entries

6.3.1.9

2 entries

3D Structure of Enzyme-Ligand-Complex (PDB) (24 results)

top print hide

Show 3D Structure of Enzyme-Ligand-Complex (PDB) (24 entries)

EC NUMBER

ENZYME 3D STRUCTURE

3.5.1.78

3a2y, 3D-view

3.5.1.78

3o98, 3D-view

3.5.1.78

3a2y, 3D-view

3.5.1.78

3o98, 3D-view

3.5.1.78

3a2y, 3D-view

3.5.1.78

3o98, 3D-view

3.5.1.78

3a2y, 3D-view

3.5.1.78

3o98, 3D-view

3.5.1.78

3a2y, 3D-view

3.5.1.78

3o98, 3D-view

3.5.1.78

3a2y, 3D-view

3.5.1.78

3o98, 3D-view

6.3.1.8

3a2y, 3D-view

6.3.1.8

3o98, 3D-view

6.3.1.8

3a2y, 3D-view

6.3.1.8

3o98, 3D-view

6.3.1.8

3a2y, 3D-view

6.3.1.8

3o98, 3D-view

6.3.1.8

3a2y, 3D-view

6.3.1.8

3o98, 3D-view

6.3.1.8

3a2y, 3D-view

6.3.1.8

3o98, 3D-view

6.3.1.8

3a2y, 3D-view

6.3.1.8

3o98, 3D-view

3.5.1.78

12 entries

6.3.1.8

12 entries

Enzyme Kinetic Parameters

k_cat Value (Turnover Number) (8 results)

top print hide

Show Turnover Number (8 entries)

EC NUMBER

TURNOVER NUMBER [1/S]

TURNOVER NUMBER MAXIMUM [1/S]

COMMENTARY

LITERATURE

3.5.1.78

2.1

-

-

969

4.4.1.5

83

-

-

681984

4.4.1.5

105

-

with phenylglyoxal

678043

4.4.1.5

161

-

with methylglyoxal

678043

4.4.1.5

1590

-

-

681984

6.3.1.9

2.8

-

pH 8.0

652306

6.3.1.9

8.7

-

pH 7.2, 25°C, recombinant trypanothione synthase

662446

6.3.1.9

10

-

-

971

4.4.1.5

4 entries

6.3.1.9

3 entries

K_M Value (15 results)

top print hide

Show KM Value (15 entries)

EC NUMBER

KM VALUE [MM]

KM VALUE MAXIMUM [MM]

COMMENTARY

LITERATURE

3.5.1.78

0.5

-

pH 7.3, amidase activity

649733

3.5.1.78

0.9

-

-

969

3.5.1.78

5.5

-

C173A mutant amidase fragment

31903

4.4.1.5

0.008

-

with methylglyoxal

678043

4.4.1.5

0.014

-

with phenylglyoxal

678043

4.4.1.5

0.064

-

-

681984

4.4.1.5

0.148

-

-

681984

3.5.1.78

3 entries

4.4.1.5

4 entries

6.3.1.8

0.5

-

pH 7.3, 25°C, amidase activity

649733

6.3.1.9

0.012

-

recombinant enzyme, pH 8.0, 25°C, HEPES buffer

727951

6.3.1.9

0.016

-

recombinant enzyme, pH 8.0, 37°C, HEPES buffer

727951

6.3.1.9

0.02

-

-

971

6.3.1.9

0.032

-

recombinant enzyme, pH 7.0, 37°C, phosphate buffer

727951

6.3.1.9

0.04

-

pH 7.7, 25°C, recombinant trypanothione synthase

662802

6.3.1.9

0.066

-

pH 8.0

652306

6.3.1.9

0.48

-

pH 7.2, 25°C, recombinant trypanothione synthase

662446

6.3.1.9

7 entries

References & Links

Literature References (31)

top print hide

Show Reference (31 entries)

BRENDA REFERENCE ID

PUBMED ID

TITLE

YEAR

AUTHORS

JOURNAL

VOLUME

PAGES

962

-

Glutathionylspermidine synthetase

1971

Tabor, H.; Tabor, C.W.

Methods Enzymol.

17

815-817

963

-

Biochemical studies on protein folding chaperones (HSP90 and cyclophilin) and on trypanosomal enzymes (trypanothione and glutathionylspermidine synthetases) (heat shock protein)

1995

Nadeau, K.C.

Diss. Abstr. Int. B

56

3744

964

1304372

Purification of glutathionylspermidine and trypanothione synthetase from Crithidia fasciculata

1992

Smith, K.; Nadeau, K.; Bradley, M.; Walsh, C.; Fairlamb, A.H.

Protein Sci.

1

874-883

965

9677355

Cloning and characterization of the two enzymes responsible for trypanothione biosynthesis in Crithidia fasciculata

1998

Tetaud, E.; Manai, F.; Barrett, M.P.; Nadeau, K.; Walsh, C.T.; Fairlamb, A.H.

J. Biol. Chem.

273

19383-19390

966

9041518

Characterization of the peptide substrate specificity of glutathionylspermidine synthetase from Crithidia fasciculata

1997

De Craecker, S.; Verbruggen, C.; Rajan, P.; Smith, K.; Haemers, A.; Fairlamb, A.H.

Mol. Biochem. Parasitol.

84

25-32

967

9384533

Aldehyde and phosphinate analogs of glutathione and glutathionylspermidine: potent, selective binding inhibitors of the E. coli bifunctional glutathionylspermidine synthetase/amidase

1997

Lin, C.H.; Chen, S.; Kwon, D.S.; Coward, J.K.; Walsh, C.T.

Chem. Biol.

4

859-866

968

9371250

Design, synthesis, and biochemical evaluation of phosphonate and phosphonamidate analogs of glutathionylspermidine as inhibitors of glutathionylspermidine synthetase/amidase from Escherichia coli

1997

Chen, S.; Lin, C.H.; Kwon, D.S.; Walsh, C.T.; Coward, J.K.

J. Med. Chem.

40

3842-3850

969

7775463

Glutathionylspermidine metabolism in Escherichia coli. Purification, cloning, overproduction, and characterization of a bifunctional glutathionylspermidine synthetase/amidase

1995

Bollinger, J.M.; Kwon, D.S.; Huisman, G.W.; Kolter, R.; Walsh, C.T.

J. Biol. Chem.

270

14031-14041

971

2354163

Biosynthesis of the trypanosomatid metabolite trypanothione: purification and characterization of trypanothione synthetase from Crithidia fasciculata

1990

Henderson, G.B.; Yamaguchi, M.; Novoa, L.; Fairlamb, A.H.; Cerami, A.

Biochemistry

29

3924-3929

31903

9398217

Evidence for a glutathionyl-enzyme intermediate in the amidase activity of the bifunctional glutathionylspermidine synthetase/amidase from Escherichia coli

1997

Lin, C.H.; Kwon, D.S.; Bollinger, J.M.; Walsh, C.T.

Biochemistry

36

14930-14938

649733

12049631

Characterization of recombinant glutathionylspermidine synthetase/amidase from Crithidia fasciculata

2002

Oza, S.L.; Ariyanayagam, M.R.; Fairlamb, A.H.

Biochem. J.

364

679-686

650561

12217358

Glutathione-like tripeptides as inhibitors of glutathionylspermidine synthetase. Part 2: Substitution of the glycine part

2002

Amssoms, K.; Oza, S.L.; Augustyns, K.; Yamani, A.; Lambeir, A.M.; Bal, G.; Van der Veken, P.; Fairlamb, A.H.; Haemers, A.

Bioorg. Med. Chem. Lett.

12

2703-2705

650657

-

Detection by HPLC of a trypanothione synthetase activity in vitro from Entamoeba histolytica

1999

Ondarza, R.N.; Hernandez, E.; Iturbe, A.; Hurtado, G.; Tamayo, E.M.

Biotechnol. Appl. Biochem.

30

41-45

652306

12121990

A Single Enzyme Catalyses Formation of Trypanothione from Glutathione and Spermidine in Trypanosoma cruzi

2002

Oza, S.L.; Tetaud, E.; Ariyanayagam, M.R.; Warnon, S.S.; Fairlamb, A.H.

J. Biol. Chem.

277

35853-35861

661011

16008527

Phenotypic analysis of trypanothione synthetase knockdown in the African trypanosome

2005

Ariyanayagam, M.R.; Oza, S.L.; Guther, M.L.S.; Fairlamb, A.H.

Biochem. J.

391

425-432

661810

15110394

Valdiation of Trypanosoma brucei trypanothione synthetase as drug target

2004

Comini, M.A.; Guerrero, S.A.; Haile, S.; Menge, U.; Lunsdorf, H.; Flohe, L.

Free Radic. Biol. Med.

36

1289-1302

662446

15537651

Trypanothione synthesis in Crithidia revisited

2005

Comini, M.; Menge, U.; Wissing, J.; Flohe, L.

J. Biol. Chem.

280

6850-6860

662802

15610825

Trypanothione biosynthesis in Leishmania major

2005

Oza, S.L.; Shaw, M.P.; Wyllie, S.; Fairlamb, A.H.

Mol. Biochem. Parasitol.

139

107-116

678043

16958620

Trypanothione-dependent glyoxalase I in Trypanosoma cruzi

2006

Greig, N.; Wyllie, S.; Vickers, T.J.; Fairlamb, A.H.

Biochem. J.

400

217-223

681984

16430697

Specificity of the trypanothione-dependent Leishmania major glyoxalase I: structure and biochemical comparison with the human enzyme

2006

Ariza, A.; Vickers, T.J.; Greig, N.; Armour, K.A.; Dixon, M.J.; Eggleston, I.M.; Fairlamb, A.H.; Bond, C.S.

Mol. Microbiol.

59

1239-1248

692049

18533363

Microbial glyoxalase enzymes: metalloenzymes controlling cellular levels of methylglyoxal

2008

Sukdeo, N.; Honek, J.F.

Drug Metabol. Drug Interact.

23

29-50

712459

20530482

Protein S-thiolation by Glutathionylspermidine (Gsp): the role of Escherichia coli Gsp synthetase/amidase in redox regulation

2010

Chiang, B.Y.; Chen, T.C.; Pai, C.H.; Chou, C.C.; Chen, H.H.; Ko, T.P.; Hsu, W.H.; Chang, C.Y.; Wu, W.F.; Wang, A.H.; Lin, C.H.

J. Biol. Chem.

285

25345-25353

716863

21226054

Structure and mechanism of Escherichia coli glutathionylspermidine amidase belonging to the family of cysteine; histidine-dependent amidohydrolases/peptidases

2011

Pai, C.H.; Wu, H.J.; Lin, C.H.; Wang, A.H.

Protein Sci.

20

557-566

727554

23106382

Escherichia coli glutathionylspermidine synthetase/amidase: phylogeny and effect on regulation of gene expression

2013

Chattopadhyay, M.K.; Chen, W.; Tabor, H.

FEMS Microbiol. Lett.

338

132-140

727627

23097746

Comparison of the functions of glutathionylspermidine synthetase/amidase from E. coli and its predicted homologues YgiC and YjfC

2012

Sui, L.; Warren, J.C.; Russell, J.P.; Stourman, N.V.

Int. J. Biochem. Mol. Biol.

3

302-312

727951

23814051

Dissecting the catalytic mechanism of Trypanosoma brucei trypanothione synthetase by kinetic analysis and computational modeling

2013

Leroux, A.E.; Haanstra, J.R.; Bakker, B.M.; Krauth-Siegel, R.L.

J. Biol. Chem.

288

23751-23764

728592

23451087

Molecular dynamics reveal binding mode of glutathionylspermidine by trypanothione synthetase

2013

Koch, O.; Cappel, D.; Nocker, M.; Jaeger, T.; Flohe, L.; Sotriffer, C.A.; Selzer, P.M.

PLoS ONE

8

e56788

744910

29127710

Buthionine sulfoximine is a multitarget inhibitor of trypanothione synthesis in Trypanosoma cruzi

2017

Vazquez, C.; Mejia-Tlachi, M.; Gonzalez-Chavez, Z.; Silva, A.; Rodriguez-Zavala, J.S.; Moreno-Sanchez, R.; Saavedra, E.

FEBS Lett.

591

3881-3894

744964

24853758

Genetic and chemical analyses reveal that trypanothione synthetase but not glutathionylspermidine synthetase is essential for Leishmania infantum

2014

Sousa, A.F.; Gomes-Alves, A.G.; Benitez, D.; Comini, M.A.; Flohe, L.; Jaeger, T.; Passos, J.; Stuhlmann, F.; Tomas, A.M.; Castro, H.

Free Radic. Biol. Med.

73

229-238

746173

27070550

Identification of novel chemical scaffolds inhibiting trypanothione synthetase from pathogenic trypanosomatids

2016

Benitez, D.; Medeiros, A.; Fiestas, L.; Panozzo-Zenere, E.A.; Maiwald, F.; Prousis, K.C.; Roussaki, M.; Calogeropoulou, T.; Detsi, A.; Jaeger, T.; Sarlauskas, J.; Peterlin Masic, L.; Kunick, C.; Labadie, G.R.; Flohe, L.; Comini, M.A.

PLoS Negl. Trop. Dis.

10

e0004617

746270

24901644

Stage-dependent expression and up-regulation of trypanothione synthetase in amphotericin B resistant Leishmania donovani

2014

Equbal, A.; Suman, S.S.; Anwar, S.; Singh, K.P.; Zaidi, A.; Sardar, A.H.; Das, P.; Ali, V.

PLoS ONE

9

e97600

Links to other databases for glutathionylspermidine

top print hide

Show Links (1 entry)

ChEBI

PubChem

-