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Information on EC 4.4.1.5 - lactoylglutathione lyase and Organism(s) Escherichia coli and UniProt Accession P0AC81
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EC Tree
4.4.1.5 lactoylglutathione lyaseIUBMB Comments
Also acts on 3-phosphoglycerol-glutathione.
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Word Map
- 4.4.1.5
-
glycation
-
detoxify
- gsh
-
dicarbonyls
- erythrocyte
- d-lactate
- adduct
- dismutase
-
endproducts
- rage
- s-transferase
- mellitus
-
methylglyoxal-induced
-
glyoxalases
-
byproduct
- hyperglycemia
-
glutathione-dependent
- phosphoglucomutase
-
metalloenzyme
- hemithioacetal
-
mg-induced
- hla-a
- aldose
- 3-deoxyglucosone
-
enediolate
-
d-lactic
-
pentosidine
-
cyclopentyl
- mdhar
- haptoglobin
- aminoguanidine
- diesters
- monodehydroascorbate
- 6-phosphogluconate
-
anti-glycation
- dehydroascorbate
-
anxiety-like
-
gsh-dependent
- pyridoxamine
- analysis
- trypanothione
- medicine
- drug development
The taxonomic range for the selected organisms is: Escherichia coli
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
glyoxalase i, glyoxalase 1, glo-1, glo-i, glo i, glyoxalase-i, glyoxalase-1, gly-i, lactoylglutathione lyase, glyoxylase i, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
aldoketomutase
-
-
-
-
GLXI
glyoxalase I
glyoxylase I
-
-
-
-
ketone-aldehyde mutase
-
-
-
-
lyase, lactoylglutathione
-
-
-
-
methylglyoxalase
-
-
-
-
methylglyoxylase
-
-
-
-
S-D-lactoylglutathione methylglyoxal lyase
-
-
-
-
GLXI
-
-
-
-
glyoxalase I
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
(R)-S-lactoylglutathione = glutathione + 2-oxopropanal
methylglyoxal and glutathione form an intermediate, the hemithioacetal, which is catalyzed to S-D-lactoylglutathione by GlxI. Subsequently S-D-lactoylglutathione is hydrolyzed to D-lactate and glutathione by GlxII (EC 3.1.2.6)
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SYSTEMATIC NAME
IUBMB Comments
(R)-S-lactoylglutathione methylglyoxal-lyase (isomerizing; glutathione-forming)
Also acts on 3-phosphoglycerol-glutathione.
CAS REGISTRY NUMBER
COMMENTARY
9033-12-9
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
glutathione + methylglyoxal
S-lactoylglutathione
the substrat is the hemithioacetal of methylglyoxal and glutathione
-
-
?
glutathione-methylglyoxal hemithioacetal
(R)-S-lactoylglutathione
-
-
-
?
methylglyoxal + glutathione
(R)-S-lactoylglutathione
first step in the glyoxalase system, detoxification of methylglyoxal
-
-
r
methylglyoxal + glutathione
S-((R)-lactoyl)glutathione
methylglyoxal and glutathione form an intermediate, the hemithioacetal, which is catalyzed to S-D-lactoylglutathione by GlxI. Subsequently S-D-lactoylglutathione is hydrolyzed to D-lactate and glutathione by GlxII (EC 3.1.2.6)
-
-
?
glutathione + methylglyoxal
(R)-S-lactoylglutathione
-
the reverse reaction from the hemithioacetate intermediate proceeds non-enzymatically
-
-
?
glutathione-methylglyoxal hemithioacetal
(R)-S-lactoylglutathione
-
glutathione-methylglyoxal hemithioacetal is formed non-enzymatically from methylglyoxal and glutathione
-
?
glutathione-methylglyoxal hemithioacetal
(R)-S-lactoylglutathione
-
glutathione-methylglyoxal hemithioacetal is formed non-enzymatically from methylglyoxal and glutathione
-
?
glutathione-methylglyoxal hemithioacetal
(R)-S-lactoylglutathione
-
glutathione-methylglyoxal hemithioacetal is formed non-enzymatically from methylglyoxal and glutathione
-
?
additional information
?
-
the enzyme is a part of the glyoxalase system that is composed of EC 4.4.1.5 and EC 3.1.2.6. The glyoxalase system converts toxic alpha-keto aldehydes into their corresponding nontoxic 2-hydroxycarboxylic acids
-
-
?
additional information
?
-
-
the enzyme is a part of the glyoxalase system that is composed of EC 4.4.1.5 and EC 3.1.2.6. The glyoxalase system converts toxic alpha-keto aldehydes into their corresponding nontoxic 2-hydroxycarboxylic acids
-
-
?
additional information
?
-
-
the glyoxalase system is an ubiquitous pathway for the detoxification of highly reactive ketoaldehydes
-
-
?
additional information
?
-
the glyoxalase system is an ubiquitous pathway for the detoxification of highly reactive ketoaldehydes
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
methylglyoxal + glutathione
(R)-S-lactoylglutathione
first step in the glyoxalase system, detoxification of methylglyoxal
-
-
r
glutathione-methylglyoxal hemithioacetal
(R)-S-lactoylglutathione
-
glutathione-methylglyoxal hemithioacetal is formed non-enzymatically from methylglyoxal and glutathione
-
?
glutathione-methylglyoxal hemithioacetal
(R)-S-lactoylglutathione
-
glutathione-methylglyoxal hemithioacetal is formed non-enzymatically from methylglyoxal and glutathione
-
?
glutathione-methylglyoxal hemithioacetal
(R)-S-lactoylglutathione
-
glutathione-methylglyoxal hemithioacetal is formed non-enzymatically from methylglyoxal and glutathione
-
?
additional information
?
-
the enzyme is a part of the glyoxalase system that is composed of EC 4.4.1.5 and EC 3.1.2.6. The glyoxalase system converts toxic alpha-keto aldehydes into their corresponding nontoxic 2-hydroxycarboxylic acids
-
-
?
additional information
?
-
-
the enzyme is a part of the glyoxalase system that is composed of EC 4.4.1.5 and EC 3.1.2.6. The glyoxalase system converts toxic alpha-keto aldehydes into their corresponding nontoxic 2-hydroxycarboxylic acids
-
-
?
additional information
?
-
-
the glyoxalase system is an ubiquitous pathway for the detoxification of highly reactive ketoaldehydes
-
-
?
additional information
?
-
the glyoxalase system is an ubiquitous pathway for the detoxification of highly reactive ketoaldehydes
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Co2+
Ni2+
Cd2+
Co2+
Fe2+
Mn2+
Ni2+
Zn2+
additional information
Co2+
GlxI is a Ni2+/Co2+-activated homodimeric protein containing two symmetric, and dually metallated active sites as characterized by X-ray studies
Ni2+
GlxI is a Ni2+/Co2+-activated homodimeric protein containing two symmetric, and dually metallated active sites as characterized by X-ray studies
Cd2+
activation, Km: 0.0089 mM, Vmax: 0.043 mmol/min/mg, kcat: 21 1/s
Cd2+
-
can partially substitute for Zn2+, the proton-transfer step is partially rate-limiting for the Cd2+ -substituted enzyme utilizing alpha-deuterophenylglyoxal as substrate
Co2+
activation, Km: 0.012 mM, Vmax: 0.213 mmol/min/mg, kcat: 106 1/s
Ni2+
highest reactivation activity, Km: 0.027 mM, Vmax: 0.676 mmol/min/mg, kcat: 338 1/s
additional information
-
not activated by Zn2+, Zn2+ can bind to the enzyme, but the resulting enzyme is inactive. Mg2+ does not bind to the apoGlxI as determined by isothermal titration calorimetry
additional information
not activated by Zn2+, Zn2+ can bind to the enzyme, but the resulting enzyme is inactive. Mg2+ does not bind to the apoGlxI as determined by isothermal titration calorimetry
additional information
-
no activation by Ni2+. The two metals stabilize the transition state, possibly an enediol(ate)-like transition state, to different extents and/or there is a differential contribution to a mechanism that requires exchange of the water ligands on the metal with the oxygens of the substrate hemithioacetal, homodimeric in nature with two subunits identified in the structure,with each active site being formed by residues from each of the two subunits and two water (or hydroxide) molecules completing the octahedral metal-co-ordination environment
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Zn2+
inactivation of gly I, metal can bind to the enzyme gly I, but the resulting enzyme is inactive
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
the KM value with Cd2+ is 0.0089 mM
-
additional information
additional information
the KM value with Cd2+ is 0.0089 mM
-
additional information
additional information
-
the KM value with Co2+ is 0.012 mM
-
additional information
additional information
the KM value with Co2+ is 0.012 mM
-
additional information
additional information
-
the KM value with Fe2+ is 0.01 mM
-
additional information
additional information
the KM value with Fe2+ is 0.01 mM
-
additional information
additional information
-
the KM value with Mn2+ is 0.01 mM
-
additional information
additional information
the KM value with Mn2+ is 0.01 mM
-
additional information
additional information
-
the KM value with Ni2+ is 0.027 mM
-
additional information
additional information
the KM value with Ni2+ is 0.027 mM
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
the turnover number with Cd2+ is 21 s
-
additional information
additional information
the turnover number with Cd2+ is 21 s
-
additional information
additional information
-
the turnover number with Co2+ is 106 s
-
additional information
additional information
the turnover number with Co2+ is 106 s
-
additional information
additional information
-
the turnover number with Fe2+ is 56 s
-
additional information
additional information
the turnover number with Fe2+ is 56 s
-
additional information
additional information
-
the turnover number with Mn2+ is 60 s
-
additional information
additional information
the turnover number with Mn2+ is 60 s
-
additional information
additional information
-
the turnover number with Ni2+ is 338 s
-
additional information
additional information
the turnover number with Ni2+ is 338 s
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
homodimer
the homodimeric GlxI of Escherichia coli consists of two identical polypeptide chains with one tryptophan on each chain on position 61, with two symmetrical active sites where one metal ion has been observed in each individual active site. One active site binds to the Ni2+ ion, and the other active site is observed to be more selelective for a potent inhibitor
homodimer
homodimer
GlxI, containing activating metals all have two water molecules bound to the active site metal along with four protein side chains making up the homodimer of the enzyme: His5 A-subunit, Glu56 A-subunit, His74 B-subunit, Glu122 B-subunit. The inactive Zn2+-bound enzyme has the same four protein side chains bound to the metal, but only one water molecule is coordinated to the Zn2+
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
the homodimeric GlxI of Escherichia coli consists of two identical polypeptide chains with one tryptophan on each chain on position 61, with two symmetrical active sites wehre one metal ion has been observed in each individual active site. One active site binds to the Ni2+ ion, and the other active site is observed to be more selelective for a potent inhibitor
a comparison of the X-ray structures of the Escherichia coli GlxI reconstituted with Zn2+ (inactive) and with the activating metals Co2+, Cd2+, Ni2+ reveals that all activating metals have an octahedral environment, but the Zn2+-bound form of the enzyme results in antrigonal bipyramidal five-coordinate environment around the metal. GlxI, containing activating metals all have two water molecules bound to the active site metal along with four protein side chains making up the homodimer of the enzyme: His5 A-subunit, Glu56 A-subunit, His74 B-subunit, Glu122 B-subunit. The inactive Zn2+-bound enzyme has the same four protein side chains bound to the metal, but only one water molecule is coordinated to the Zn2+
crystallization of apo GlxI and GlxI complexed with Ni2+ Co2+, Cd2+, Zn2+, and seleno-L-methionine-Ni2+ by vapor diffusion in hanging drops, 0.005 ml protein solution at 12-37 mg/ml is mixed with an equal volume of well solution containing 5-10% polyethylene glycol 1000 and 5-10% polyethylene glycol 8000, crystals diffract to 1.5-2.5 A, Zn2+-GlxI complex has trigonal bipyramidal instead of octhedral coordination with Ni2+, Co2+ and Cd2+ and is inactive
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
H74Q
the native His74 metal ligand substituted with a Gln residue, maintains a homodimeric quaternary structure in solution as does the wild-type enzyme
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant overproduction of gly1 in Escherichia coli in the presence of Ni2+ in the growth medium results in the formation of active enzyme, overproduction of in the presence of Zn2+ in the growth medium results in the formation of inactive enzyme
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
vander Jagt, D.L.
The glyoxalase system
Coenzymes and cofactors, Glutathione, Chem. Biochem. Med. Aspects Pt. A (Dolphin D, Poulson R, Avromonic O, eds. ) John Wiley & Sons, New York
3
597-641
1989
Saccharomyces cerevisiae, Oryctolagus cuniculus, Escherichia coli, Ovis aries, Homo sapiens, Mus musculus, Rattus norvegicus, Rhodospirillum rubrum, Sus scrofa
-
Deswal, R.; Sopory, S.K.
Biochemical and immunochemical characterization of Brassica juncea glyoxalase I
Phytochemistry
49
2245-2253
1998
Arabidopsis sp., Brassica rapa subsp. oleifera, Brassica juncea, Brassica nigra, Brassica oleracea, Cajanus cajan, Candida albicans, Escherichia coli, Hordeum vulgare, Mus musculus, Sorghum bicolor, Triticum aestivum, Zea mays
Clugston, S.L.; Barnard, J.F.J.; Kinach, R.; Miedema, D.; Ruman, R.; Daub, E.; Honek, J.F.
Overproduction and characterization of a dimeric non-zinc glyoxalase I from Escherichia coli: evidence for optimal activation by nickel ions
Biochemistry
37
8754-8763
1998
Escherichia coli (P0AC81), Escherichia coli, Escherichia coli MG1655/pGL10 (P0AC81)
Creighton, D.J.; Hamilton, D.S.
Brief history of glyoxalase I and what we have learned about metal ion-dependent, enzyme-catalyzed isomerizations
Arch. Biochem. Biophys.
387
1-10
2001
Saccharomyces cerevisiae, Escherichia coli, Homo sapiens
Clugston, S.L.; Yajima, R.; Honek, J.F.
Investigation of metal binding and activation of Escherichia coli glyoxalase I: kinetic, thermodynamic and mutagenesis studies
Biochem. J.
377
309-316
2004
Escherichia coli
He, M.M.; Clugston, S.L.; Honek, J.F.; Matthews, B.W.
Determination of the Structure of Escherichia coli Glyoxalase I Suggests a Structural Basis for Differential Metal Activation
Biochemistry
39
8719-8727
2000
Escherichia coli
Su, Z.; Sukdeo, N.; Honek, J.F.
15N-1H HSQC NMR evidence for distinct specificity of two active sites in Escherichia coli glyoxalase I
Biochemistry
47
13232-13241
2008
Escherichia coli (P0AC81), Escherichia coli
Sukdeo, N.; Honek, J.F.
Microbial glyoxalase enzymes: metalloenzymes controlling cellular levels of methylglyoxal
Drug Metabol. Drug Interact.
23
29-50
2008
Escherichia coli, Escherichia coli (P0AC81), Homo sapiens, Homo sapiens (Q04760), Leishmania braziliensis, Leishmania donovani, Leishmania major, Leishmania sp., Neisseria meningitidis, Neisseria meningitidis (P0A0T3), Plasmodium falciparum, Pseudomonas aeruginosa, Pseudomonas aeruginosa (Q9HU72), Pseudomonas aeruginosa (Q9HY85), Pseudomonas aeruginosa (Q9I5L8), Pseudomonas putida, Pseudomonas putida (Q88GF8), Trypanosoma cruzi, Yersinia pestis
Honek, J.F.
Bacterial glyoxalase I enzymes: structural and biochemical investigations
Biochem. Soc. Trans.
42
479-484
2014
Saccharomyces cerevisiae, Clostridium acetobutylicum, Escherichia coli, Homo sapiens, Leishmania donovani, Leishmania infantum, Leishmania major, Neisseria meningitidis, Yersinia pestis, Plasmodium falciparum, Pseudomonas aeruginosa, Pseudomonas putida, Pseudomonas fluorescens, Pseudomonas syringae, Trypanosoma cruzi
EXTERNAL LINKS (specific for EC-Number 4.4.1.5)
Transporter Classification Database (TCDB): 9.A.15.3.1
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