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Information on EC 1.21.98.4 - PqqA peptide cyclase
for references in articles please use BRENDA:EC1.21.98.4
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EC Tree 1 Oxidoreductases
1.21 Catalysing the reaction X-H + Y-H = X-Y
1.21.98 With other, known, physiological acceptors
1.21.98.4 PqqA peptide cyclase
IUBMB Comments
This bacterial enzyme, which is a member of the radical SAM protein family, catalyses the formation of a C-C bond between C-4 of glutamate and C-3 of tyrosine residues of the PqqA protein (which are separated by three amino acid residues). This is the first enzymic step in the biosynthesis of the bacterial enzyme cofactor pyrroloquinoline quinone (PQQ). The reaction is dependent on the presence of a reductant (flavodoxin) and the accessory protein PqqD.
The enzyme appears in viruses and cellular organisms
Reaction Schemes
show+
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a PqqA peptide
+
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a PqqA peptide with linked Glu-Tyr residues
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Synonyms
pqqE, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
pqqE
pqqE
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a PqqA peptide + S-adenosyl-L-methionine = a PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
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-
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PATHWAY SOURCE
PATHWAYS
MetaCyc
pyrroloquinoline quinone biosynthesis
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SYSTEMATIC NAME
IUBMB Comments
PqqA peptide:S-adenosyl-L-methionine oxidoreductase (cyclizing)
This bacterial enzyme, which is a member of the radical SAM protein family, catalyses the formation of a C-C bond between C-4 of glutamate and C-3 of tyrosine residues of the PqqA protein (which are separated by three amino acid residues). This is the first enzymic step in the biosynthesis of the bacterial enzyme cofactor pyrroloquinoline quinone (PQQ). The reaction is dependent on the presence of a reductant (flavodoxin) and the accessory protein PqqD.
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
a PqqA peptide + S-adenosyl-L-methionine
a PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
PqqA peptide + S-adenosyl-L-methionine
PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
a PqqA peptide + S-adenosyl-L-methionine
a PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
Substrates: -
Products: -
Products: -
?
a PqqA peptide + S-adenosyl-L-methionine
a PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
Substrates: the enzyme is involved in the pyrroloquinoline quinone biosynthetic pathway. PqqE is a radical S-adenosylmethionine protein with a C-terminal SPASM domain, and is proposed to catalyze the formation of a carbon-carbon bond between the glutamate and tyrosine side chains of the peptide substrate PqqA
Products: -
Products: -
?
a PqqA peptide + S-adenosyl-L-methionine
a PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
Substrates: -
Products: -
Products: -
?
a PqqA peptide + S-adenosyl-L-methionine
a PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
Substrates: PqqE is a radical S-adenosylmethionine protein with a C-terminal SPASM domain, and is proposed to catalyze the formation of a carbon-carbon bond between the glutamate and tyrosine side chains of the peptide substrate PqqA
Products: -
Products: -
?
a PqqA peptide + S-adenosyl-L-methionine
a PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
Substrates: the enzyme catalyzes the carbon-carbon bond formation between a Glu15 and Tyr19 side chain within the small peptide substrate PqqA. Intramolecular cross-linking reaction between PqqA residues
Products: -
Products: -
?
a PqqA peptide + S-adenosyl-L-methionine
a PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
Substrates: the enzyme is involved in the pyrroloquinoline quinone biosynthetic pathway. PqqE is a radical S-adenosylmethionine protein with a C-terminal SPASM domain, and is proposed to catalyze the formation of a carbon-carbon bond between the glutamate and tyrosine side chains of the peptide substrate PqqA
Products: -
Products: -
?
a PqqA peptide + S-adenosyl-L-methionine
a PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
Substrates: PqqE is a radical S-adenosylmethionine protein with a C-terminal SPASM domain, and is proposed to catalyze the formation of a carbon-carbon bond between the glutamate and tyrosine side chains of the peptide substrate PqqA
Products: -
Products: -
?
a PqqA peptide + S-adenosyl-L-methionine
a PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
Substrates: -
Products: -
Products: -
?
a PqqA peptide + S-adenosyl-L-methionine
a PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
Substrates: the enzyme catalyzes the carbon-carbon bond formation between a Glu15 and Tyr19 side chain within the small peptide substrate PqqA. Intramolecular cross-linking reaction between PqqA residues
Products: -
Products: -
?
PqqA peptide + S-adenosyl-L-methionine
PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
Substrates: -
Products: -
Products: -
?
PqqA peptide + S-adenosyl-L-methionine
PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
Substrates: the reaction takes place with PqqA bound to the peptide binding protein PqqD3, and involves formation of a new carbon bond between glutamate and tyrosine catalyzed by PqqE
Products: -
Products: -
?
PqqA peptide + S-adenosyl-L-methionine
PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
Substrates: the reaction employs a chaperone protein PqqD to deliver the peptide substrate PqqA to the enzyme
Products: -
Products: -
?
PqqA peptide + S-adenosyl-L-methionine
PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
Substrates: -
Products: -
Products: -
?
PqqA peptide + S-adenosyl-L-methionine
PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
-
Substrates: the reaction is catalyzed by the enzyme PqqE in the presence of the chaperone PqqD
Products: -
Products: -
?
PqqA peptide + S-adenosyl-L-methionine
PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
Substrates: -
Products: -
Products: -
?
PqqA peptide + S-adenosyl-L-methionine
PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
Substrates: the reaction takes place with PqqA bound to the peptide binding protein PqqD3, and involves formation of a new carbon bond between glutamate and tyrosine catalyzed by PqqE
Products: -
Products: -
?
PqqA peptide + S-adenosyl-L-methionine
PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
Substrates: the reaction employs a chaperone protein PqqD to deliver the peptide substrate PqqA to the enzyme
Products: -
Products: -
?
PqqA peptide + S-adenosyl-L-methionine
PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
Substrates: -
Products: -
Products: -
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
a PqqA peptide + S-adenosyl-L-methionine
a PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
PqqA peptide + S-adenosyl-L-methionine
PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
a PqqA peptide + S-adenosyl-L-methionine
a PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
Substrates: -
Products: -
Products: -
?
a PqqA peptide + S-adenosyl-L-methionine
a PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
Substrates: the enzyme is involved in the pyrroloquinoline quinone biosynthetic pathway. PqqE is a radical S-adenosylmethionine protein with a C-terminal SPASM domain, and is proposed to catalyze the formation of a carbon-carbon bond between the glutamate and tyrosine side chains of the peptide substrate PqqA
Products: -
Products: -
?
a PqqA peptide + S-adenosyl-L-methionine
a PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
Substrates: -
Products: -
Products: -
?
a PqqA peptide + S-adenosyl-L-methionine
a PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
Substrates: the enzyme is involved in the pyrroloquinoline quinone biosynthetic pathway. PqqE is a radical S-adenosylmethionine protein with a C-terminal SPASM domain, and is proposed to catalyze the formation of a carbon-carbon bond between the glutamate and tyrosine side chains of the peptide substrate PqqA
Products: -
Products: -
?
a PqqA peptide + S-adenosyl-L-methionine
a PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
Substrates: -
Products: -
Products: -
?
PqqA peptide + S-adenosyl-L-methionine
PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
Substrates: -
Products: -
Products: -
?
PqqA peptide + S-adenosyl-L-methionine
PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
Substrates: the reaction takes place with PqqA bound to the peptide binding protein PqqD3, and involves formation of a new carbon bond between glutamate and tyrosine catalyzed by PqqE
Products: -
Products: -
?
PqqA peptide + S-adenosyl-L-methionine
PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
Substrates: the reaction employs a chaperone protein PqqD to deliver the peptide substrate PqqA to the enzyme
Products: -
Products: -
?
PqqA peptide + S-adenosyl-L-methionine
PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
Substrates: -
Products: -
Products: -
?
PqqA peptide + S-adenosyl-L-methionine
PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
-
Substrates: the reaction is catalyzed by the enzyme PqqE in the presence of the chaperone PqqD
Products: -
Products: -
?
PqqA peptide + S-adenosyl-L-methionine
PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
Substrates: -
Products: -
Products: -
?
PqqA peptide + S-adenosyl-L-methionine
PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
Substrates: the reaction takes place with PqqA bound to the peptide binding protein PqqD3, and involves formation of a new carbon bond between glutamate and tyrosine catalyzed by PqqE
Products: -
Products: -
?
PqqA peptide + S-adenosyl-L-methionine
PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
Substrates: the reaction employs a chaperone protein PqqD to deliver the peptide substrate PqqA to the enzyme
Products: -
Products: -
?
PqqA peptide + S-adenosyl-L-methionine
PqqA peptide with linked Glu-Tyr residues + 5'-deoxyadenosine + L-methionine
Substrates: -
Products: -
Products: -
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
iron-sulfur centre
the enzyme contains three Fe-S centers, at least two of which are present as [4Fe-4S]. PqqD interacts specifically with the radical SAM enzyme PqqE, causing a perturbation in the electronic environment around the [4Fe-4S]+ clusters
[2Fe-2S]-center
the enzyme contains one 2Fe-2S cluster (AuxI cluster)
[4Fe-4S]-center
the enzyme contains three 4Fe-4S clusters (RS, AuxII and AuxI clusters)
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
PqqD
PqqD is a peptide Chaperone that forms a ternary complex with the radical S-adenosylmethionine protein PqqE. The stoichiometry of the MePqqD and MePqqE interaction is 1:1. PqqD is a 10 kDa protein with an unknown function, but is essential for production of pyrroloquinoline quinone
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PqqD
PqqE activity is dependent on the accessory protein PqqD. The intramolecular cross-linking reaction that occurs between PqqA residues is dependent on PqqE, the peptide chaperone PqqD, and the flavodoxin reductase system
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
metabolism
the enzyme is involved in the pyrroloquinoline quinone biosynthetic pathway
metabolism
first enzyme in the biosynthetic pathway of the redox cofactor pyrroloquinoline quinone
metabolism
first enzyme in the biosynthetic pathway of the redox cofactor pyrroloquinoline quinone
metabolism
-
the enzyme is involved in the pyrroloquinoline quinone biosynthetic pathway
-
metabolism
-
first enzyme in the biosynthetic pathway of the redox cofactor pyrroloquinoline quinone
-
Show AA Sequence and Transmembrane Helices (3009 entries)
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Please use the AA Sequence and Transmembrane Helices Search for a specific query.
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
sitting drop vapor diffusion method, using 0.2 M magnesium formate, 20% (w/v) polyethylene glycol 3350
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C268H
the mutation selectively incorporates a [4Fe-4S] cluster, catalyzes an enhancement of uncoupled S-adenosyl-L-methionine cleavage relative to wild type and eliminates the detectable peptide cross-linked product
C32A/C35A
the mutations cause a decrease in the iron loading of the enzyme, and abolish both the reductive cleavage of S-adenosyl-L-methionine and cross-link formation on PqqA peptide
D319A
the mutant leads to a decrease in iron loading (around 9 Fe per protein) and is also unable to cross-link PqqA peptide
D319C
the mutant exhibits slightly lower S-adenosyl-L-methionine cleavage and peptide modification activity than the wild type protein
D319H
the mutant maintains cross-linking and S-adenosyl-L-methionine cleavage activities at a similar or higher level than the wild type protein
C32A/C35A
-
the mutations cause a decrease in the iron loading of the enzyme, and abolish both the reductive cleavage of S-adenosyl-L-methionine and cross-link formation on PqqA peptide
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D319A
-
the mutant leads to a decrease in iron loading (around 9 Fe per protein) and is also unable to cross-link PqqA peptide
-
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Ni-NTA resin column chromatography, ultrafiltration, and PD-10 gel filtration
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) or Rosetta 2 (DE3) cells
expressed in Escherichia coli BL21(DE3) or Rosetta 2 (DE3) cells
expressed in Escherichia coli BL21(DE3) or Rosetta 2 (DE3) cells
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Wecksler, S.; Stoll, S.; Iavarone, A.; Imsand, E.; Tran, H.; Britt, R.; Klinman, J.
Interaction of PqqE and PqqD in the pyrroloquinoline quinone (PQQ) biosynthetic pathway links PqqD to the radical SAM superfamily
Chem. Commun. (Camb.)
46
7031-7033
2010
Klebsiella pneumoniae (P27507)
brenda
Latham, J.; Iavarone, A.; Barr, I.; Juthani, P.; Klinman, J.
PqqD is a novel peptide chaperone that forms a ternary complex with the radical S-adenosylmethionine protein PqqE in the pyrroloquinoline quinone biosynthetic pathway
J. Biol. Chem.
290
12908-12918
2015
Methylorubrum extorquens (P71517), Methylorubrum extorquens ATCC 14718 (P71517)
brenda
Barr, I.; Latham, J.; Iavarone, A.; Chantarojsiri, T.; Hwang, J.; Klinman, J.
Demonstration that the radical S-adenosylmethionine (SAM) enzyme PqqE catalyzes de novo carbon-carbon cross-linking within a peptide substrate PqqA in the presence of the peptide chaperone PqqD
J. Biol. Chem.
291
8877-8884
2016
Methylorubrum extorquens (P71517), Methylorubrum extorquens ATCC 14718 (P71517)
brenda
Barr, I.; Stich, T.; Gizzi, A.; Grove, T.; Bonanno, J.; Latham, J.; Chung, T.; Wilmot, C.; Britt, R.; Almo, S.; Klinman, J.
X-ray and EPR characterization of the auxiliary Fe-S clusters in the radical SAM enzyme PqqE
Biochemistry
57
1306-1315
2018
Methylorubrum extorquens (P71517), Methylorubrum extorquens ATCC 14718 (P71517)
brenda
Tao, L.; Zhu, W.; Klinman, J.; Britt, R.
Electron paramagnetic resonance spectroscopic identification of the Fe-S clusters in the SPASM domain-containing radical SAM enzyme PqqE
Biochemistry
58
5173-5187
2019
Methylorubrum extorquens (P71517), Methylorubrum extorquens ATCC 14718 (P71517)
brenda
Zhu, W.; Walker, L.; Tao, L.; Iavarone, A.; Wei, X.; Britt, R.; Elliott, S.; Klinman, J.
Structural properties and catalytic implications of the SPASM domain iron-sulfur clusters in Methylorubrum extorquens PqqE
J. Am. Chem. Soc.
142
12620-12634
2020
Methylorubrum extorquens (P71517)
brenda
Martins, A.; Latham, J.; Martel, P.; Barr, I.; Iavarone, A.; Klinman, J.
A two-component protease in Methylorubrum extorquens with high activity toward the peptide precursor of the redox cofactor pyrroloquinoline quinone
J. Biol. Chem.
294
15025-15036
2019
Methylorubrum extorquens
brenda
Zhu, W.; Martins, A.; Klinman, J.
Methods for expression, purification, and characterization of PqqE, a radical SAM enzyme in the PQQ biosynthetic pathway
Methods Enzymol.
606
389-420
2018
Klebsiella pneumoniae (P27507), Methylorubrum extorquens (P71517), Methylorubrum extorquens ATCC 14718 (P71517)
brenda
EXTERNAL LINKS (specific for EC-Number 1.21.98.4)
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