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Information on EC 1.3.3.11 - pyrroloquinoline-quinone synthase and Organism(s) Klebsiella pneumoniae and UniProt Accession P27505
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1.3.3.11 pyrroloquinoline-quinone synthaseIUBMB Comments
So far only a single turnover of the enzyme has been observed, and the pyrroloquinoline quinone remains bound to it. It is not yet known what releases the product in the bacterium.
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Word Map
- 1.3.3.11
-
quinoproteins
- methanol
-
prosthetic
- dehydrogenases
- radiodurans
- extorquens
-
methylobacterium
-
pqq-containing
- deinococcus
- calcoaceticus
-
acinetobacter
- synthesis
- biotechnology
- analysis
The taxonomic range for the selected organisms is: Klebsiella pneumoniae
The expected taxonomic range for this enzyme is: Bacteria, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Archaea
Reaction Schemes
Synonyms
pqqc/d, quinoprotein dehydrogenase, pyrroloquinoline-quinone synthase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
PqqC
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
6-(2-amino-2-carboxyethyl)-7,8-dioxo-1,2,3,4,7,8-hexahydroquinoline-2,4-dicarboxylate + 3 O2 = 4,5-dioxo-4,5-dihydro-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylate + 2 H2O2 + 2 H2O
PqqC is part of a complex of six enzymes that act together in pyrroloquinoline-quinone synthesis: PqqA serves as a complex precursor for for pyrroloquinoline-quinone synthesis, PqqB is not directly required for pyrroloquinoline-quinone biosynthesis, but a carrier and responsible for its transport across the plasma-membrane into the periplasm, PqqC does not contain a redox-active metal or other cofactor and is responsible for the last cyclization and oxidation steps in pyrroloquinoline-quinone synthesis, PqqD has three possible functions: first, it could play a role in the release of pyrroloquinoline-quinone from PqqC, second it could be involved in binding of PqqB to PqqC, third it could function as the dioxygenase in the pathway, PqqE is a family member of radical S-adenosylmethionine enzymes and catalyzes a radical driven C-C bond formation required to link the glutamate and tyrosine moieties at atoms C9 and C9a of pyrroloquinoline-quinone, PqqF recognizes and cleaves all four peptide bonds in PqqA
6-(2-amino-2-carboxyethyl)-7,8-dioxo-1,2,3,4,7,8-hexahydroquinoline-2,4-dicarboxylate + 3 O2 = 4,5-dioxo-4,5-dihydro-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylate + 2 H2O2 + 2 H2O
reaction mechanism consisting of a series of base catalyzed proton abstractions followed by quinoid/quinol tautomerizations and oxidations, overview
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PATHWAY SOURCE
PATHWAYS
-
-
SYSTEMATIC NAME
IUBMB Comments
6-(2-amino-2-carboxyethyl)-7,8-dioxo-1,2,3,4,7,8-hexahydroquinoline-2,4-dicarboxylate:oxygen oxidoreductase (cyclizing)
So far only a single turnover of the enzyme has been observed, and the pyrroloquinoline quinone remains bound to it. It is not yet known what releases the product in the bacterium.
CAS REGISTRY NUMBER
COMMENTARY
353484-42-1
-
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
3a-(2-amino-2-carboxyethyl)-4,5-dioxo-4,5,6,7,8,9-hexahydroquinoline-7,9-dicarboxylic acid + O2
4,5-dioxo-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylate + H2O2 + H2O
6-(2-amino-2-carboxyethyl)-7,8-dioxo-1,2,3,4,7,8-hexahydroquinoline-2,4-dicarboxylate + 3 O2
4,5-dioxo-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylate + 2 H2O2 + 2 H2O
-
-
-
?
3a-(2-amino-2-carboxyethyl)-4,5-dioxo-4,5,6,7,8,9-hexahydroquinoline-7,9-dicarboxylic acid + O2
4,5-dioxo-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylate + H2O2 + H2O
-
-
-
-
?
6-(2-amino-2-carboxyethyl)-7,8-dioxo-1,2,3,4,5,6,7,8,-octahydroquinoline-2,4-dicarboxylate + O2
4,5-dioxo-3a,4,5,6,7,8,9,9b-octahydro-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylate + H2O2 + H2O
-
-
-
-
?
6-(2-amino-2-carboxyethyl)-7,8-dioxo-1,2,3,4,7,8-hexahydroquinoline-2,4-dicarboxylate + 3 O2
4,5-dioxo-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylate + 2 H2O2 + 2 H2O
-
-
-
?
additional information
?
-
-
catalyzes the final step of PQQ formation, which involves a ring closure and an overall eight-electron oxidation of 3a-(2-amino-2-carboxyethyl)-4,5-dioxo-4,5,6,7,8,9-hexahydroquinoline-7,9-dicarboxylic acid in the absence of a redox-active metal or cofactor
-
-
?
3a-(2-amino-2-carboxyethyl)-4,5-dioxo-4,5,6,7,8,9-hexahydroquinoline-7,9-dicarboxylic acid + O2
4,5-dioxo-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylate + H2O2 + H2O
-
-
-
?
3a-(2-amino-2-carboxyethyl)-4,5-dioxo-4,5,6,7,8,9-hexahydroquinoline-7,9-dicarboxylic acid + O2
4,5-dioxo-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylate + H2O2 + H2O
-
the product is pyrroloquinoline quinone (PQQ)
-
?
3a-(2-amino-2-carboxyethyl)-4,5-dioxo-4,5,6,7,8,9-hexahydroquinoline-7,9-dicarboxylic acid + O2
4,5-dioxo-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylate + H2O2 + H2O
synthesis of the pyrroloquinoline quinone (PQQ), that serves as prosthetic group for many bacterial enzymes
the product is pyrroloquinoline quinone (PQQ)
-
?
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
3a-(2-amino-2-carboxyethyl)-4,5-dioxo-4,5,6,7,8,9-hexahydroquinoline-7,9-dicarboxylic acid + O2
4,5-dioxo-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylate + H2O2 + H2O
synthesis of the pyrroloquinoline quinone (PQQ), that serves as prosthetic group for many bacterial enzymes
the product is pyrroloquinoline quinone (PQQ)
-
?
6-(2-amino-2-carboxyethyl)-7,8-dioxo-1,2,3,4,7,8-hexahydroquinoline-2,4-dicarboxylate + 3 O2
4,5-dioxo-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylate + 2 H2O2 + 2 H2O
-
-
-
?
6-(2-amino-2-carboxyethyl)-7,8-dioxo-1,2,3,4,5,6,7,8,-octahydroquinoline-2,4-dicarboxylate + O2
4,5-dioxo-3a,4,5,6,7,8,9,9b-octahydro-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylate + H2O2 + H2O
-
-
-
-
?
6-(2-amino-2-carboxyethyl)-7,8-dioxo-1,2,3,4,7,8-hexahydroquinoline-2,4-dicarboxylate + 3 O2
4,5-dioxo-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylate + 2 H2O2 + 2 H2O
-
-
-
?
additional information
?
-
-
catalyzes the final step of PQQ formation, which involves a ring closure and an overall eight-electron oxidation of 3a-(2-amino-2-carboxyethyl)-4,5-dioxo-4,5,6,7,8,9-hexahydroquinoline-7,9-dicarboxylic acid in the absence of a redox-active metal or cofactor
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
PqqC catalyzes the last step of pyrroloquinoline quinone biogenesis which involves a ring closure and an eight-electron oxidation of the substrate 3a-(2-amino-2-carboxyethyl)-4,5-dioxo-4,5,6,7,8,9-hexahydroquinoline-7,9-dicarboxylic acid
physiological function
pyrroloquinoline quinone, i.e. 4,5-dihydro-4,5-dioxo-1Hpyrrolo[2,3-f]quinoline-2,7,9-tricarboxylic acid, PQQ, synthesized by the enzyme, is a bacterial cofactor in numerous alcohol dehydrogenases including methanol dehydrogenase and glucose dehydrogenase
additional information
additional information
an all atom model of the quinoprotein dehydrogenase PqqC in complex with 4,5-dihydro-4,5-dioxo-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylic acid (PQQ) and O2, solvated with TIP3 water in periodic boxes, is subjected to random-acceleration molecular dynamics (RAMD) showing that O2 leaves the active binding pocket, in front of PQQ, to get to the solvent, as easily as with a variety of other O2-activating enzymes, O2 carriers, and gas-sensing proteins. The shortest pathway, orthogonal to the center of the mean plane of PQQ, is largely preferred by O2 over pathways slightly deviating from this line. These observations challenge the interpretation of an impermeable active binding pocket of PqqC-PQQ, as drawn from both X-ray diffraction data of the crystal at low temperature and physiological experimentation. Key residues for the minor O2 gates are 1. Q155, L158, R177, and R17, 2. E188, and L191, and 3. D83 and Q182, or the main O2 egress involving residues P151, L180, and A183, modeling, overview
additional information
the enzyme has 14 conserved active site residues, which are in close contact with bound substrate pyrroloquinoline quinone. It exhibits a stepwise process in which substrate binding leads to the generation of the closed protein conformation, with the latter playing a critical role in O2 binding and catalysis
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
additional information
the enzyme folds into a compact seven-helix bundle, which provide the scaffold for an active site cavity
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinant enzyme mutants H154S/PQQ Y175F/PQQ Y175S/R179S in complex with intermediate 3a-(2-amino-2-carboxyethyl)-4,5-dioxo-4,5,6,7,8,9-hexahydroquinoline-7,9-dicarboxylic acid, sitting drop-vapor diffusion method, optimized conditions for each mutant: 0.1 M HEPES, pH 7.0, 0.5% w/v PEG 8000 for mutant H154S/PQQ complex, 0.2 M ammonium sulfate, 0.1 M Bis-Tris, pH 6.5, 25% w/v PEGl 3350 for mutant Y175F/PQQ complex, and 0.2 M sodium chloride, 0.1 M Tris, pH 8.5, 25% w/v PEG 3350 for mutant R179S/Y175S/intermediate complex, all at 20°C, X-ray diffraction structure determination and analysis at 1.3-2.35 A resolution
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
H154S
site-directed mutagenesis, active site mutant, even with substrate PQQ bound, the enzyme is still in the open conformation with helices alpha5b and alpha6 unfolded and the active site solvent accessible, no product formation
R179S/Y175S
site-directed mutagenesis, active site mutant, the mutant shows an open conformation with a reaction intermediate trapped in the active site, the intermediate is tricyclic but nonplanar, implying that it has not undergone oxidatio, R179S/Y175S shows acceptable substrate complex crystals
Y175F
site-directed mutagenesis, active site mutant, the mutant shows a closed conformation indicating that Y175 is not required for the conformational change, no product formation
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged wild-type and mutant enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and gel filtration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene pqqC, expression of wild-type and mutant enzymes as His-tagged enzyme in Escherichia coli strain BL21(DE3)
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Magnusson, O.T.; Toyama, H.; Saeki, M.; Rojas, A.; Reed, J.C.; Liddington, R.C.; Klinman, J.P.; Schwarzenbacher, R.
Quinone biogenesis: Structure and mechanism of PqqC, the final catalyst in the production of pyrroloquinoline quinone
Proc. Natl. Acad. Sci. USA
101
7913-7918
2004
Klebsiella pneumoniae (P27505)
Schwarzenbacher, R.; Stenner-Liewen, F.; Liewen, H.; Reed, J.C.; Liddington, R.C.
Crystal structure of PqqC from Klebsiella pneumoniae at 2.1 ANG resolution
Proteins
56
401-403
2004
Klebsiella pneumoniae (P27505)
Toyama, H.; Nishibayashi, E.; Saeki, M.; Adachi, O.; Matsushita, K.
Factors required for the catalytic reaction of PqqC/D which produces pyrroloquinoline quinone
Biochem. Biophys. Res. Commun.
354
290-295
2007
Escherichia coli, Klebsiella pneumoniae, Methylorubrum extorquens, Methylorubrum extorquens ATCC 14718 / DSM 1338 / JCM 2805 / NCIMB 9133 / AM1
Magnusson, O.T.; RoseFigura, J.M.; Toyama, H.; Schwarzenbacher, R.; Klinman, J.P.
Pyrroloquinoline quinone biogenesis: characterization of PqqC and its H84N and H84A active site variants
Biochemistry
46
7174-7186
2007
Klebsiella pneumoniae
Puehringer, S.; Metlitzky, M.; Schwarzenbacher, R.
The pyrroloquinoline quinone biosynthesis pathway revisited: a structural approach
BMC Biochem.
9
8-8
2008
Escherichia coli, Klebsiella pneumoniae (P27505), Pseudomonas aeruginosa
Puehringer, S.; RoseFigura, J.; Metlitzky, M.; Toyama, H.; Klinman, J.P.; Schwarzenbacher, R.
Structural studies of mutant forms of the PQQ-forming enzyme PqqC in the presence of product and substrate
Proteins
78
2554-2562
2010
Klebsiella pneumoniae (A6T9H1), Klebsiella pneumoniae MGH 78578 (A6T9H1)
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