Information on EC 4.3.2.5 - peptidylamidoglycolate lyase

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The expected taxonomic range for this enzyme is: Coelomata

EC NUMBER
COMMENTARY
4.3.2.5
-
RECOMMENDED NAME
GeneOntology No.
peptidylamidoglycolate lyase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
peptidylamidoglycolate = peptidyl amide + glyoxylate
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
amidine-lyase reaction
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
peptidylamidoglycolate peptidyl-amide-lyase (glyoxylate-forming)
The enzyme acts on the product of the reaction catalysed by EC 1.14.17.3 peptidylglycine monooxygenase, thus removing a terminal glycine residue and leaving a des-glycine peptide amide.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
alpha-hydroxyglycine amidating dealkylase
-
-
-
-
dPAL1 gene product
Q9V5E1
-
dPAL2 gene product
Q9W1L5
-
HGAD
-
-
lyase, peptidyl-alpha hydroxyglycine
-
-
-
-
PAL
-
-
PAL
Q9V5E1, Q9W1L5
-
PAL
P19021
-
PAL
P14925
-
peptidyl-alpha-hydroxyglycine alpha-amidating lyase
-
-
-
-
peptidyl-alpha-hydroxyglycine alpha-amidating lyase
Q9V5E1
-
peptidyl-alpha-hydroxyglycine alpha-amidating lyase
Q9W1L5
-
peptidyl-alpha-hydroxyglycine alpha-amidating lyase
P14925
-
peptidylamidoglycolate lyase
P19021
-
PGL
-
-
rPAL gene product
P14925
-
CAS REGISTRY NUMBER
COMMENTARY
131689-50-4
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
EC 1.14.17.3 (PHM) and EC 4.3.2.5 (PAL) are part of a bifunctional protein
-
-
Manually annotated by BRENDA team
expression in COS-7 cells, the two enzymes EC 1.14.17.3 and EC 4.3.2.5 are generated from a common precursor protein encoded by a single mRNA
-
-
Manually annotated by BRENDA team
soluble, bifunctional form PAM-3, expression in a human embryonic kidney cell line that lacks regulated secretory granules, EC 1.14.17.3 and EC 4.3.2.5 are contained within the bifunctional peptidylglycine alpha-amidation monooxygenase, PAM
-
-
Manually annotated by BRENDA team
Sprague-Dawley, EC 1.14.17.3 (PHM) and EC 4.3.2.5 (PAL) are part of a bifunctional, integral membrane protein precursor, peptidylglycine alpha-amidating monooxygenase, PAM, which consists of independent catalytic domains separated from each other and from the putative transmembrane domain by flexible regions accessible to attack by a wide variety of endoproteinases
-
-
Manually annotated by BRENDA team
truncated type A enzyme which catalyzes a two-step reaction involving an initial hydroxylation of peptidyl-Gly followed by conversion of the peptidyl-alpha-hydroxyglycine intermediate to the amidated product, enzyme is secreted into the medium from mouse C127 cells transfected with the rat MTC cDNA encoding the truncated type A enzyme
-
-
Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(R)-2-phenylbutyl-alpha-hydroxy-Gly
(R)-2-phenylbutyl-NH2 + glyoxylate
show the reaction diagram
-
-
-
-
?
(R)-O-acetyl-mandelyl-alpha-hydroxyglycine
(R)-O-acetyl-mandelyl-NH2 + glyoxylate
show the reaction diagram
-
-
-
-
?
(S)-2-phenylbutyl-alpha-hydroxy-Gly
(S)-2-phenylbutyl-NH2 + glyoxylate
show the reaction diagram
-
-
-
-
?
(S)-O-acetyl-mandelyl-alpha-hydroxyglycine
(S)-O-acetyl-mandelyl-NH2 + glyoxylate
show the reaction diagram
-
-
-
-
?
acetyl-D-Phe-alpha-hydroxyglycine
acetyl-D-Phe-NH2 + glyoxylate
show the reaction diagram
-
-
-
-
?
acetyl-L-Phe-alpha-hydroxyglycine
acetyl-L-Phe-NH2 + glyoxylate
show the reaction diagram
-
-
-
-
?
alpha-hydroxybenzoylglycine
benzamide + glyoxylate
show the reaction diagram
-
-
-
-
?
alpha-hydroxyglycine-extended peptide
peptidyl amide + glyoxylate
show the reaction diagram
-
-
-
-
-
alpha-hydroxyglycine-extended peptide
peptidyl amide + glyoxylate
show the reaction diagram
-
-
-
-
-
alpha-hydroxyglycine-extended peptide
peptidyl amide + glyoxylate
show the reaction diagram
-
-
-
-
?
alpha-hydroxyglycine-extended peptide
peptidyl amide + glyoxylate
show the reaction diagram
-
-
-
?
alpha-hydroxyglycine-extended peptide
peptidyl amide + glyoxylate
show the reaction diagram
-
-
-
?
alpha-hydroxyglycine-extended peptide
peptidyl amide + glyoxylate
show the reaction diagram
-
the alpha-hydroxyglycine moiety produced by EC 1.14.17.3 is of the S configuration
-
-
?
alpha-N-acetyl-Tyr-Val-alpha-hydroxyglycine
alpha-N-acetyl-Tyr-Val-NH2 + glyoxylate
show the reaction diagram
Q9V5E1, Q9W1L5
-
-
-
?
alpha-N-acetyl-Tyr-Val-alpha-hydroxyglycine
alpha-N-acetyl-Tyr-Val-NH2 + glyoxylate
show the reaction diagram
P14925
-
-
-
?
dansyl-Tyr-Val-alpha-hydroxyglycine
dansyl-Tyr-Val-NH2 + glyoxylate
show the reaction diagram
-
-
-
?
N-2,4,6-trinitrophenyl-D-Tyr-L-Val-(S)-alpha-hydroxy-Gly
N-2,4,6-trinitrophenyl-D-Tyr-L-Val-amide + glyoxylate
show the reaction diagram
P19021
-
-
-
?
N-benzoyl-alpha-hydroxy-Gly
benzamide + glyoxylate
show the reaction diagram
-
-
-
-
?
Nalpha-acetyl-Tyr-Val-alpha-hydroxyglycine
Nalpha-acetyl-Tyr-Val-NH2 + glyoxylate
show the reaction diagram
-
-
-
-
-
Nalpha-acetyl-Tyr-Val-alpha-hydroxyglycine
Nalpha-acetyl-Tyr-Val-NH2 + glyoxylate
show the reaction diagram
-
-
-
-
?
Nalpha-acetyl-Tyr-Val-alpha-hydroxyglycine
Nalpha-acetyl-Tyr-Val-NH2 + glyoxylate
show the reaction diagram
-
-
-
?
Nalpha-acetyl-Tyr-Val-alpha-hydroxyglycine
Nalpha-acetyl-Tyr-Val-NH2 + glyoxylate
show the reaction diagram
-
-
-
-
?
peptidylamidoglycolate
peptidyl amide + glyoxylate
show the reaction diagram
Q9V5E1, Q9W1L5
-
-
-
?
peptidylamidoglycolate
peptidyl amide + glyoxylate
show the reaction diagram
P14925
-
-
-
?
trinitrophenyl-D-Tyr-L-Val-alpha-hydroxy-Gly
trinitrophenyl-D-Tyr-L-Val-NH2 + glyoxylate
show the reaction diagram
-
-
-
-
?
trinitrophenyl-D-Tyr-L-Val-alpha-hydroxy-Gly
trinitrophenyl-D-Tyr-L-Val-NH2 + glyoxylate
show the reaction diagram
-
-
-
-
?
trinitrophenyl-D-Tyr-Val-alpha-hydroxy-Gly
trinitrophenyl-D-Tyr-Val-NH2 + glyoxylate
show the reaction diagram
-
-
-
?
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
N-2,4,6-trinitrophenyl-D-Tyr-L-Val-(S)-alpha-hydroxy-Gly
N-2,4,6-trinitrophenyl-D-Tyr-L-Val-amide + glyoxylate
show the reaction diagram
P19021
-
-
-
?
peptidylamidoglycolate
peptidyl amide + glyoxylate
show the reaction diagram
Q9V5E1, Q9W1L5
-
-
-
?
peptidylamidoglycolate
peptidyl amide + glyoxylate
show the reaction diagram
P14925
-
-
-
?
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
additional information
-
no cofactor requirement
-
additional information
-
no cofactor requirement
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Cd2+
Q9V5E1, Q9W1L5
activates the enzyme; activates the enzyme
Cd2+
P14925
activates the enzyme
Cd2+
P19021
activates, binding of Co2+ or Cd2+ to empty zinc-binding sites on PAL
Co2+
Q9V5E1, Q9W1L5
activates the enzyme; activates the enzyme
Co2+
P14925
activates the enzyme
Co2+
P19021
activates, binding of Co2+ or Cd2+ to empty zinc-binding sites on PAL
Cu2+
P19021
activates
Ni2+
P19021
activates
Zn2+
-
0.7 mol per mol enzyme
Zn2+
P19021
activates, binding of Co2+ or Cd2+ to empty zinc-binding sites on PAL
Mn2+
P19021
activates, wild-type
additional information
P19021
the reaction is greatly accelerated by addition of such divalent metals as Mn2+, Co2+, Ni2+, Cu2+, Zn2+, and Cd2+, and the restoration of PAL activity by divalent metals
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(R)-2-phenylbutyl-alpha-hydroxy-Gly
-
-
(S)-2-phenylbutyl-alpha-hydroxy-Gly
-
-
2-mercaptoethanol
-
-
acetylmethionyl pyruvate
-
competitive inhibition of PGL domain of full expressed enzyme: AE and monofunctional lyase: PGL
acetylphenylalanyl pyruvate
-
competitive inhibition of PGL domain of full expressed enzyme: AE and monofunctional lyase: PGL
acetyltyrosyl pyruvate
-
competitive inhibition of PGL domain of full expressed enzyme: AE and monofunctional lyase: PGL
diethyl dicarbonate
-
-
EDTA
-
divalent metals restore activity
EDTA
-
addition of 0.5-1 M reduces activity to 50%, Ca2+, Mn2+, Co2+ or Ni2+ restore activity
EDTA
Q9V5E1, Q9W1L5
1 mM; 1 mM
EGTA
-
addition of 0.5-1 M reduces activity to 50%, Ca2+, Mn2+, Co2+ or Ni2+ restore activity
HCl
-
0.5 M guanidinium HCl reduces activity to 28%
K2SO4
-
150 mM
NaCl
-
150 mM
o-phenanthroline
-
-
phenylacetyl-alpha-hydroxy-Gly
-
competitive inhibition
Phenylglyoxal
-
-
Urea
-
addition of 1 M urea reduces activity to 58%
KCl
-
150 mM
additional information
-
relatively resistant to thiol reagents and urea
-
additional information
-
-
-
additional information
-
the inhibitors of PAM: acetyl-L-Phe-acetic acid and [(4-methoxybenzoyl)oxy]acetic acid show no effect of the KM of the monofunctional lyase: PGL
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
Cd2+
Q9V5E1, Q9W1L5
;
Co2+
Q9V5E1, Q9W1L5
;
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.3
-
(R)-2-phenylbutyl-alpha-hydroxy-Gly
-
37C, pH 6.5
2.6
-
(R)-O-acetyl-mandelyl-alpha-hydroxyglycine
-
37C, pH 6.5
0.33
-
(S)-2-phenylbutyl-alpha-hydroxy-Gly
-
37C, pH 6.5
0.56
-
(S)-O-acetyl-mandelyl-alpha-hydroxyglycine
-
37C, pH 6.5
0.5
-
acetyl-D-Phe-alpha-hydroxyglycine
-
37C, pH 6.5
0.23
-
acetyl-L-Phe-alpha-hydroxyglycine
-
37C, pH 6.5
0.013
-
alpha-N-Acetyl-Tyr-Val-alpha-hydroxyglycine
P14925
-
0.045
-
alpha-N-Acetyl-Tyr-Val-alpha-hydroxyglycine
Q9V5E1, Q9W1L5
-
0.238
-
alpha-N-Acetyl-Tyr-Val-alpha-hydroxyglycine
Q9V5E1, Q9W1L5
-
0.035
0.048
Dansyl-Tyr-Val-alpha-hydroxyglycine
-
37C, pH 7.0
0.0215
-
N-2,4,6-trinitrophenyl-D-Tyr-L-Val-(S)-alpha-hydroxy-Gly
P19021
pH 6.0, 25C, wild-type enzyme
0.0887
-
N-2,4,6-trinitrophenyl-D-Tyr-L-Val-(S)-alpha-hydroxy-Gly
P19021
pH 6.0, 25C, metal-depleted enzyme
0.46
-
N-benzoyl-alpha-hydroxy-Gly
-
37C, pH 6.5
0.0102
-
Nalpha-Acetyl-Tyr-Val-alpha-hydroxyglycine
-
37C, pH 5.5, E707Q
0.0139
-
Nalpha-Acetyl-Tyr-Val-alpha-hydroxyglycine
-
37C, pH 5.5, recombinant wild-type
0.0156
-
Nalpha-Acetyl-Tyr-Val-alpha-hydroxyglycine
-
37C, pH 5.5, H690A
0.0214
-
Nalpha-Acetyl-Tyr-Val-alpha-hydroxyglycine
-
37C, pH 5.5, D705N
0.0231
-
Nalpha-Acetyl-Tyr-Val-alpha-hydroxyglycine
-
37C, pH 5.5, H585A
0.034
-
Nalpha-Acetyl-Tyr-Val-alpha-hydroxyglycine
-
37C, pH 7.4, with endoprotease Arg-C digested PAM-3 protein
0.037
-
Nalpha-Acetyl-Tyr-Val-alpha-hydroxyglycine
-
37C, pH 7.4, undigested PAM-3 protein
0.038
-
Nalpha-Acetyl-Tyr-Val-alpha-hydroxyglycine
-
37C, pH 7
0.0985
-
Nalpha-Acetyl-Tyr-Val-alpha-hydroxyglycine
-
37C, pH 5.5, H786A
0.33
-
Nalpha-Acetyl-Tyr-Val-alpha-hydroxyglycine
-
37C, pH 5.5
0.014
-
trinitrophenyl-D-Tyr-L-Val-alpha-hydroxy-Gly
-
37C, pH 6.6, PGL domain of transmembrane truncated enzyme: dAE
0.018
-
trinitrophenyl-D-Tyr-L-Val-alpha-hydroxy-Gly
-
37C, pH 6.6, PGL domain of full expressed enzyme: AE
0.019
-
trinitrophenyl-D-Tyr-L-Val-alpha-hydroxy-Gly
-
37C, pH 6.6, monofunctional lyase: PGL
0.027
-
trinitrophenyl-D-Tyr-L-Val-alpha-hydroxy-Gly
-
37C, pH 6.5
0.033
-
trinitrophenyl-D-Tyr-L-Val-alpha-hydroxy-Gly
-
37C, pH 6.6
0.0023
0.004
dansyl-Tyr-Val-Gly
-
37C, pH 6
additional information
-
additional information
P19021
apparent second-order rate constants at different pHs
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
3.2
-
N-2,4,6-trinitrophenyl-D-Tyr-L-Val-(S)-alpha-hydroxy-Gly
P19021
pH 6.0, 25C, metal-depleted enzyme
25.7
-
N-2,4,6-trinitrophenyl-D-Tyr-L-Val-(S)-alpha-hydroxy-Gly
P19021
pH 6.0, 25C, wild-type enzyme
86
-
Nalpha-Acetyl-Tyr-Val-alpha-hydroxyglycine
-
37C, pH 7.4, with endoprotease Arg-C digested PAM-3 protein
92
-
Nalpha-Acetyl-Tyr-Val-alpha-hydroxyglycine
-
37C, pH 7.4, undigested PAM-3 protein
220
-
Nalpha-Acetyl-Tyr-Val-alpha-hydroxyglycine
-
37C, pH 7
380
-
Nalpha-Acetyl-Tyr-Val-alpha-hydroxyglycine
-
37C, pH 5.5
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.31
-
(R)-2-phenylbutyl-alpha-hydroxy-Gly
-
37C, pH 6.5
0.28
-
(S)-2-phenylbutyl-alpha-hydroxy-Gly
-
37C, pH 6.5
3.2
-
acetylmethionyl pyruvate
-
37C, pH 6.6, monofunctional lyase: PGL
4.8
-
acetylmethionyl pyruvate
-
37C, pH 6.6, PGL domain of full expressed enzyme: AE
0.049
-
acetylphenylalanyl pyruvate
-
37C, pH 6.6, monofunctional lyase: PGL
0.071
-
acetylphenylalanyl pyruvate
-
37C, pH 6.6, PGL domain of full expressed enzyme: AE
0.55
-
acetyltyrosyl pyruvate
-
37C, pH 6.6, monofunctional lyase: PGL
0.92
-
acetyltyrosyl pyruvate
-
37C, pH 6.6, PGL domain of full expressed enzyme: AE
0.77
-
phenylacetyl-alpha-hydroxy-Gly
-
37C, pH 6.5
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.25
0.32
-
dansyl-Tyr-Val-Gly as substrate
0.53
-
-
Sephacryl S-300 purification step
4.5
8.3
-
dansyl-Tyr-Val-alpha-hydroxyglycine as substrate
57.24
-
-
affinity chromatography step II
510
-
-
Mono Q pool A, after concentration
12000
-
-
Superose 12 pool
23000
-
-
PGL domain of full expressed enzyme: AE
76000
-
-
PGL domain of transmembrane truncated enzyme: dAE
180000
-
-
monofunctional lyase: PGL
16000000
-
-
Mono Q fraction
additional information
-
P19021
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5
-
-
-
5.5
7
P19021
-
6.5
-
Q9V5E1, Q9W1L5
-
7.5
-
Q9V5E1, Q9W1L5
-
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
25
37
P19021
assay at
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
granules; neurointermediate
Manually annotated by BRENDA team
-
enzyme is secreted into the medium from mouse C127 cells transfected with the rat MTC cDNA encoding the truncated type A enzyme
Manually annotated by BRENDA team
Q9W1L5
ap-let neuron
Manually annotated by BRENDA team
-
in A- and B-cells
Manually annotated by BRENDA team
-
in A-, B- and D-cells
Manually annotated by BRENDA team
-
in peripheral islet and B-cells
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
secretory granular fraction
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
38000
-
-
gel filtration
43900
-
Q9V5E1, Q9W1L5
monomer, secreted, rhodopsin-tagged protein, calculated from amino acid sequence
44400
-
Q9V5E1, Q9W1L5
monomer, secreted, rhodopsin-tagged protein, calculated from amino acid sequence
45000
-
-
gel filtration
50000
-
-
PAL domain, conversion of the 50000 MW form into a 43000 MW form occurs during gel filtration
53000
-
-
gel filtration
75000
-
-
truncated type A enzyme which catalyzes a two-step reaction involving an initial hydroxylation of peptidyl-Gly followed by conversion of the peptidyl-alpha-hydroxyglycine intermediate to the amidated product
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 41000, SDS-PAGE
?
Q9V5E1, Q9W1L5
x * 49300, rhodopsin-tagged protein, SDS-PAGE; x * 51300, rhodopsin-tagged protein, SDS-PAGE
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-20C, 50% glycerol containing 1 mg/ml bovine serum albumin
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
enzyme is encoded by the intergranular domain of the PAM-encoding cDNA
-
expression in chinese hamster ovary K-1 cells
-
expression in a human embryonic kidney cell line that lacks regulated secretory granules
-
expression in Chinese hamster ovary cells
-
expression in cultured Sf9 insect cells
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
D590N
-
no secretion
D599N
-
no secretion
D652N
-
no secretion
D705N
-
much less secretion and less active than wild-type
E707Q
-
much less secretion than wild-type
H532A
-
no secretion
H585A
-
less active than wild-type
H603A
-
no secretion
H690A
-
less active than wild-type
H697A
-
no changes in secretion an activity
H786A
-
less active than wild-type
H817A
-
no changes in secretion an activity