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Information on EC 4.1.2.50 - 6-carboxytetrahydropterin synthase and Organism(s) Escherichia coli and UniProt Accession P65870

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EC Tree
     4 Lyases
         4.1 Carbon-carbon lyases
             4.1.2 Aldehyde-lyases
                4.1.2.50 6-carboxytetrahydropterin synthase
IUBMB Comments
Binds Zn2+. Isolated from the bacteria Bacillus subtilis and Escherichia coli. The reaction is part of the biosynthesis pathway of queuosine.The enzyme from Escherichia coli can also convert 6-pyruvoyl-5,6,7,8-tetrahydropterin and sepiapterin to 6-carboxy-5,6,7,8-tetrahydropterin .
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This record set is specific for:
Escherichia coli
UNIPROT: P65870
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Word Map
The taxonomic range for the selected organisms is: Escherichia coli
The enzyme appears in selected viruses and cellular organisms
Synonyms
6-carboxytetrahydropterin synthase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6-carboxy-5,6,7,8-tetrahydropterin synthase
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6-pyruvoyltetrahydropterin synthase
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CPH4 synthase
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6-carboxy-5,6,7,8-tetrahydropterin synthase
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CPH4 synthase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
7,8-dihydroneopterin 3'-triphosphate + H2O = 6-carboxy-5,6,7,8-tetrahydropterin + acetaldehyde + triphosphate
show the reaction diagram
reaction mechanism, overview
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PATHWAY SOURCE
PATHWAYS
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SYSTEMATIC NAME
IUBMB Comments
7,8-dihydroneopterin 3'-triphosphate acetaldehyde-lyase (6-carboxy-5,6,7,8-tetrahydropterin and triphosphate-forming)
Binds Zn2+. Isolated from the bacteria Bacillus subtilis and Escherichia coli. The reaction is part of the biosynthesis pathway of queuosine.The enzyme from Escherichia coli can also convert 6-pyruvoyl-5,6,7,8-tetrahydropterin and sepiapterin to 6-carboxy-5,6,7,8-tetrahydropterin [2].
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
7,8-dihydroneopterin 3'-triphosphate + H2O
6-carboxy-5,6,7,8-tetrahydropterin + acetaldehyde + triphosphate
show the reaction diagram
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-
?
sepiapterin + H2O
?
show the reaction diagram
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-
-
?
6-pyruvoyltetrahydropterin + H2O
6-carboxy-5,6,7,8-tetrahydropterin + acetaldehyde + triphosphate
show the reaction diagram
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-
-
-
?
7,8-dihydroneopterin triphosphate + H2O
6-carboxy-5,6,7,8-tetrahydropterin + acetaldehyde + triphosphate
show the reaction diagram
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-
-
-
?
sepiapterin + H2O
6-carboxy-5,6,7,8-tetrahydropterin + acetaldehyde + triphosphate
show the reaction diagram
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?
additional information
?
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6-pyruvoyltetrahydropterin can tautomerize to sepiapterin, the hydrate of which undergoes carbon-carbon bond cleavage by an aldolase-like mechanism, followed by a tautomerization, to yield 6-carboxy-5,6,7,8-tetrahydropterin
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?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
7,8-dihydroneopterin 3'-triphosphate + H2O
6-carboxy-5,6,7,8-tetrahydropterin + acetaldehyde + triphosphate
show the reaction diagram
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-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Zn2+
contains a catalytic zinc ion
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
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QueD catalyzes the conversion of 7,8-dihydroneopterin triphosphate to 6-carboxy-5,6,7,8-tetrahydropterin, CPH4. QueD can also convert 6-pyruvoyltetrahydropterin, PPH4, and sepiapterin to CPH4
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structures of wild-type apo 6-carboxytetrahydropterin synthase and of a C27A mutant complexed with sepiapterin to 2.3 and 2.5 A resolution, respectively. The structures are highly conserved at the active site and the Zn2+ binding site. Residues Trp51 and Phe55, that are not found in mammalian 6-pyruvoyltetrahydropterin synthase keep the substrate bound by stacking it with their side chains. Replacement of these two residues by site-directed mutagenesis to the residues Met and Leu, which are only found in mammalian 6-pyruvoyltetrahydropterin synthase, converted the enzyme to the mammalian 6-pyruvoyltetrahydropterin synthase activity
hanging drop vapor diffusion method, using 5% (v/v) 2-methyl-1,3-propanediol, 0.04 M CaCl2, 0.1 M sodium acetate (pH 4.5)
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D70N/H71A
the mutant shows greatly reduced activity compared to the wild type enzyme
F55L
mutants shows 6-pyruvoyltetrahydropterin synthase activities comparable to the mammalian enzymes, with concomitant decrease in 6-carboxytetrahydropterin synthase activity
H25A/D54N
inactive
H25A/D54N/D70N/H71A
inactive
W51M
mutants shows 6-pyruvoyltetrahydropterin synthase activities comparable to the mammalian enzymes, with concomitant decrease in 6-carboxytetrahydropterin synthase activity
W51M/F55L
mutants shows 6-pyruvoyltetrahydropterin synthase activities comparable to the mammalian enzymes, with concomitant decrease in 6-carboxytetrahydropterin synthase activity
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
McCarty, R.M.; Somogyi, A.; Bandarian, V.
Escherichia coli QueD is a 6-carboxy-5,6,7,8-tetrahydropterin synthase
Biochemistry
48
2301-2303
2009
Escherichia coli
Manually annotated by BRENDA team
Seo, K.H.; Zhuang, N.; Park, Y.S.; Park, K.H.; Lee, K.H.
Structural basis of a novel activity of bacterial 6-pyruvoyltetrahydropterin synthase homologues distinct from mammalian 6-pyruvoyltetrahydropterin synthase activity
Acta Crystallogr. Sect. D
70
1212-1223
2014
Escherichia coli (P65870), Escherichia coli
Manually annotated by BRENDA team
Miles, Z.D.; Roberts, S.A.; McCarty, R.M.; Bandarian, V.
Biochemical and structural studies of 6-carboxy-5,6,7,8-tetrahydropterin synthase reveal the molecular basis of catalytic promiscuity within the tunnel-fold superfamily
J. Biol. Chem.
289
23641-23652
2014
Escherichia coli (P65870)
Manually annotated by BRENDA team