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6-carboxy-5,6,7,8-tetrahydropterin
7-carboxy-7-carbaguanine + NH3
6-carboxy-5,6,7,8-tetrahydropterin
7-carboxy-7-deazaguanine + NH3
additional information
?
-
6-carboxy-5,6,7,8-tetrahydropterin
7-carboxy-7-carbaguanine + NH3
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-
-
-
?
6-carboxy-5,6,7,8-tetrahydropterin
7-carboxy-7-carbaguanine + NH3
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-
-
?
6-carboxy-5,6,7,8-tetrahydropterin
7-carboxy-7-carbaguanine + NH3
the enzyme catalyzes a key step in the biosynthesis of 7-deazapurine containing natural products
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-
?
6-carboxy-5,6,7,8-tetrahydropterin
7-carboxy-7-carbaguanine + NH3
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-
-
?
6-carboxy-5,6,7,8-tetrahydropterin
7-carboxy-7-carbaguanine + NH3
the enzyme catalyzes a key step in the biosynthesis of 7-deazapurine containing natural products
-
-
?
6-carboxy-5,6,7,8-tetrahydropterin
7-carboxy-7-carbaguanine + NH3
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-
-
?
6-carboxy-5,6,7,8-tetrahydropterin
7-carboxy-7-carbaguanine + NH3
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-
-
?
6-carboxy-5,6,7,8-tetrahydropterin
7-carboxy-7-carbaguanine + NH3
the substrate binds perpendicular to the [4Fe-4S]-bound S-adenosyl-L-methionine cofactor, exposing its C6 hydrogen atom for abstraction and generating the binding site for Mg2+, which directly coordinates to the substrate. Substrate binding generates a metal-binding site
-
-
?
6-carboxy-5,6,7,8-tetrahydropterin
7-carboxy-7-carbaguanine + NH3
the key ring-contraction step involves a bridged intermediate rather than a ring-opening one. For the QueE-Mg2+ system, the elimination of ammonia is calculated to be rate limiting, determined by investigation at an atomistic level by using the combined quantum mechanics and molecular mechanics method
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-
?
6-carboxy-5,6,7,8-tetrahydropterin
7-carboxy-7-carbaguanine + NH3
-
-
-
?
6-carboxy-5,6,7,8-tetrahydropterin
7-carboxy-7-carbaguanine + NH3
the key ring-contraction step involves a bridged intermediate rather than a ring-opening one. For the QueE-Mg2+ system, the elimination of ammonia is calculated to be rate limiting, determined by investigation at an atomistic level by using the combined quantum mechanics and molecular mechanics method
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-
?
6-carboxy-5,6,7,8-tetrahydropterin
7-carboxy-7-carbaguanine + NH3
-
-
-
?
6-carboxy-5,6,7,8-tetrahydropterin
7-carboxy-7-carbaguanine + NH3
-
-
-
-
?
6-carboxy-5,6,7,8-tetrahydropterin
7-carboxy-7-deazaguanine + NH3
-
-
-
-
?
6-carboxy-5,6,7,8-tetrahydropterin
7-carboxy-7-deazaguanine + NH3
-
substrate from a coupled reaction with Escherichia coli CPH4 synthase
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-
?
6-carboxypterin
?
under reducing conditions that would promote the reductive cleavage of S-adenosyl-L-methionine, 6-carboxypterin is turned over to 6-deoxyadenosylpterin, presumably by radical addition of the 5'-deoxyadenosine followed by oxidative decarboxylation to the product. In the absence of the strong reductant, dithionite, the carboxylate of 6-carboxypterin is esterified to generate 6-carboxypterin-5'-deoxyadenosyl ester
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-
?
6-carboxypterin
?
under reducing conditions that would promote the reductive cleavage of S-adenosyl-L-methionine, 6-carboxypterin is turned over to 6-deoxyadenosylpterin, presumably by radical addition of the 5'-deoxyadenosine followed by oxidative decarboxylation to the product. In the absence of the strong reductant, dithionite, the carboxylate of 6-carboxypterin is esterified to generate 6-carboxypterin-5'-deoxyadenosyl ester
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-
?
additional information
?
-
-
the enzyme uses a bound [4Fe-4S]+ cluster to catalyze the reductive cleavage of S-adenosyl-L-methionine cofactor to generate methionine and a 5'-deoxyadenosyl radical, which initiates enzymatic transformations requiring H-atom abstraction
-
-
?
additional information
?
-
the enzyme uses a bound [4Fe-4S]+ cluster to catalyze the reductive cleavage of S-adenosyl-L-methionine cofactor to generate methionine and a 5'-deoxyadenosyl radical, which initiates enzymatic transformations requiring H-atom abstraction. To initiate radical chemistry, all AdoMet radical enzymes require the one-electron reduction of the [4Fe-4S] cluster. This electron is typically supplied by a flavodoxin. For the Burkholderia multivorans enzyme, more product is generated using the chemical reductant dithionite
-
-
?
additional information
?
-
-
the enzyme uses a bound [4Fe-4S]+ cluster to catalyze the reductive cleavage of S-adenosyl-L-methionine cofactor to generate methionine and a 5'-deoxyadenosyl radical, which initiates enzymatic transformations requiring H-atom abstraction. To initiate radical chemistry, all AdoMet radical enzymes require the one-electron reduction of the [4Fe-4S] cluster. This electron is typically supplied by a flavodoxin. For the Burkholderia multivorans enzyme, more product is generated using the chemical reductant dithionite
-
-
?
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6-carboxy-5,6,7,8-tetrahydropterin
7-carboxy-7-carbaguanine + NH3
6-carboxy-5,6,7,8-tetrahydropterin
7-carboxy-7-deazaguanine + NH3
-
-
-
-
?
6-carboxy-5,6,7,8-tetrahydropterin
7-carboxy-7-carbaguanine + NH3
-
-
-
-
?
6-carboxy-5,6,7,8-tetrahydropterin
7-carboxy-7-carbaguanine + NH3
-
-
-
?
6-carboxy-5,6,7,8-tetrahydropterin
7-carboxy-7-carbaguanine + NH3
the enzyme catalyzes a key step in the biosynthesis of 7-deazapurine containing natural products
-
-
?
6-carboxy-5,6,7,8-tetrahydropterin
7-carboxy-7-carbaguanine + NH3
the enzyme catalyzes a key step in the biosynthesis of 7-deazapurine containing natural products
-
-
?
6-carboxy-5,6,7,8-tetrahydropterin
7-carboxy-7-carbaguanine + NH3
-
-
-
?
6-carboxy-5,6,7,8-tetrahydropterin
7-carboxy-7-carbaguanine + NH3
-
-
-
?
6-carboxy-5,6,7,8-tetrahydropterin
7-carboxy-7-carbaguanine + NH3
-
-
-
?
6-carboxy-5,6,7,8-tetrahydropterin
7-carboxy-7-carbaguanine + NH3
-
-
-
-
?
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4Fe-4S-center
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4Fe-4S-center
S-adenosyl-L-methionine binds to the unique iron atom of a site-differentiated [4Fe-4S] cluster and is reductively cleaved to generate a 5'-deoxyadenosyl radical, which initiates turnover
4Fe-4S-center
the enzyme requires the one electron reduction of the [4Fe-4S]2+ cluster to the +1 oxidation state. This can be achieved by using a chemical reductant, such as dithionite, or a biological reducing system in which the reducing equivalents are derived from NADPH and transferred to the cluster via flavodoxin reductase and flavodoxin
S-adenosyl-L-methionine
-
dependent on. Members of the radical SAM superfamily contain a CX3CX2C-motif for binding a [4Fe-4S] cluster, which when reductively activated, cleaves SAM to 5?-deoxyadenosyl radical, which in turn initiates radical mediated transformations of the substrate
S-adenosyl-L-methionine
-
Km is 0.045 mM, the cofactor supports multiple turnovers, it is regenerated at the end of each catalytic cycle
S-adenosyl-L-methionine
the binding site is conserved despite modified enzyme fold
S-adenosyl-L-methionine
-
S-adenosyl-L-methionine-dependent radical enzyme
S-adenosyl-L-methionine
S-adenosyl-L-methionine-dependent radical enzyme
S-adenosyl-L-methionine
S-adenosyl-L-methionine-dependent radical enzyme
additional information
to initiate radical chemistry, all AdoMet radical enzymes require the one-electron reduction of the [4Fe-4S] cluster. This electron is typically supplied by a flavodoxin. For the Burkholderia multivorans enzyme, more product is generated using the chemical reductant dithionite
-
additional information
-
to initiate radical chemistry, all AdoMet radical enzymes require the one-electron reduction of the [4Fe-4S] cluster. This electron is typically supplied by a flavodoxin. For the Burkholderia multivorans enzyme, more product is generated using the chemical reductant dithionite
-
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Fe2+
-
the enzyme uses a bound [4Fe-4S]+ cluster to catalyze the reductive cleavage of S-adenosyl-L-methionine cofactor to generate methionine, a single [4Fe-4S] cluster per monomer
Fe2+
the enzyme uses a bound [4Fe-4S]+ cluster to catalyze the reductive cleavage of S-adenosyl-L-methionine cofactor to generate methionine, a single [4Fe-4S] cluster per monomer. The cluster-binding motifs of each monomer are located at opposite ends of the dimer molecule, of the Fe atoms from the cluster are coordinated by three cysteine residues from the CX14CXPhiC motif. The remaining unique Fe binds the alpha-amino and alpha-carboxyl groups of S-adenosyl-L-methionine, which adopts an anti orientation about the glycosidic bond
Mg2+
-
dependent on, Km is 0.21 mM
Mg2+
Mg2+ provides key contacts with the substrate 6-carboxy-5,6,7,8-tetrahydropterin and the product 7-carboxy-7-carbaguanine, thus anchoring the molecules in the active site. The formation of either 6-carboxypterin product is not enhanced by the presence of Mg2+
Mg2+
dependent on, the ligand environment about Mg2+ is pseudo-octahedral, with three water ligands, the substrate C4 carbonyl and C6 carboxylate oxygens, and the hydroxyl of T51
Mg2+
the Mg2+ complexation not only brings the substrate into the reactive conformation but also, once a hydrogen atom is abstracted from the substrate, holds the resultant intermediate radical in a highly strained conformation
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evolution
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QueE is a member of the radical SAM organic radical generating enzyme superfamily. Members of the radical SAM superfamily contain a CX3CX2C-motif for binding a [4Fe-4S] cluster, which when reductively activated, cleaves SAM to 5'-deoxyadenosyl radical, which in turn initiates radical mediated transformations of the substrate
evolution
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QueE is a member of the radical S-adenosyl-L-methionine superfamily, all of which use a bound [4Fe-4S]+ cluster to catalyze the reductive cleavage of S-adenosyl-L-methionine cofactor to generate methionine and a 5'-deoxyadenosyl radical, which initiates enzymatic transformations requiring H-atom abstraction
evolution
QueE is a member of the radical S-adenosyl-L-methionine superfamily, it varies from the other members in that it contains a hypermodified (beta6/alpha3) protein core and an expanded cluster-binding motif CX14CX2C, structure comparisons, overview
metabolism
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QueE is involved in the queuosine biosynthetic pathway of Bacillus subtilis
metabolism
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the enzyme catalyzes the complex heterocyclic radical-mediated conversion of 6-carboxy-5,6,7,8-tetrahydropterin to 7-carboxy-7-carbaguanine in the third step of the biosynthetic pathway to all 7-deazapurines. 7-Carboxy-7-carbaguanine is the first 7-deazapurine in the biosynthetic pathway and likely the precursor to all naturally occurring 7-deazapurine containing molecules
metabolism
the enzyme catalyzes the complex heterocyclic radical-mediated conversion of 6-carboxy-5,6,7,8-tetrahydropterin to 7-carboxy-7-carbaguanine in the third step of the biosynthetic pathway to all 7-deazapurines. 7-Carboxy-7-carbaguanine is the first 7-deazapurine in the biosynthetic pathway and likely the precursor to all naturally occurring 7-deazapurine containing molecules
metabolism
the enzyme catalyzes a key step in the biosynthesis of 7-deazapurine containing natural products
metabolism
-
the enzyme catalyzes a key step in the biosynthesis of 7-deazapurine containing natural products
-
additional information
-
mechanism of rearrangement of the enzyme
additional information
substrate binding generates a metal-binding site
additional information
-
substrate binding generates a metal-binding site
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McCarty, R.M.; Somogyi, A.; Lin, G.; Jacobsen, N.E.; Bandarian, V.
The deazapurine biosynthetic pathway revealed: in vitro enzymatic synthesis of PreQ(0) from guanosine 5-triphosphate in four steps
Biochemistry
48
3847-3852
2009
Bacillus subtilis
brenda
McCarty, R.M.; Krebs, C.; Bandarian, V.
Spectroscopic, steady-state kinetic, and mechanistic characterization of the radical SAM enzyme QueE, which catalyzes a complex cyclization reaction in the biosynthesis of 7-deazapurines
Biochemistry
52
188-198
2013
Bacillus subtilis
brenda
Dowling, D.P.; Bruender, N.A.; Young, A.P.; McCarty, R.M.; Bandarian, V.; Drennan, C.L.
Radical SAM enzyme QueE defines a new minimal core fold and metal-dependent mechanism
Nat. Chem. Biol.
10
106-112
2014
Burkholderia multivorans (A0A0H3KB22), Burkholderia multivorans
brenda
Zhu, W.; Liu, Y.
Ring contraction catalyzed by the metal-dependent radical SAM enzyme 7-carboxy-7-deazaguanine synthase from B. multivorans. theoretical insights into the reaction mechanism and the influence of metal ions
ACS Catal.
5
3953-3965
2015
Burkholderia multivorans (A0A0H3KB22), Burkholderia multivorans ATCC 17616 (A0A0H3KB22)
-
brenda
Bruender, N.A.; Young, A.P.; Bandarian, V.
Chemical and biological reduction of the radical SAM enzyme 7-carboxy-7-deazaguanine synthase
Biochemistry
54
2903-2910
2015
Bacillus subtilis (O31677), Bacillus subtilis, Bacillus subtilis 168 (O31677)
brenda
Jaeger, C.M.; Croft, A.K.
Radical reaction control in the AdoMet radical enzyme CDG synthase (QueE) consolidate, destabilize, accelerate
Chemistry
23
953-962
2017
Burkholderia multivorans (A0A0H3KB22), Burkholderia multivorans ATCC 17616 (A0A0H3KB22)
brenda
Bruender, N.A.; Grell, T.A.; Dowling, D.P.; McCarty, R.M.; Drennan, C.L.; Bandarian, V.
7-Carboxy-7-deazaguanine synthase a radical S-adenosyl-L-methionine enzyme with polar tendencies
J. Am. Chem. Soc.
139
1912-1920
2017
Bacillus subtilis (O31677), Bacillus subtilis 168 (O31677)
brenda
Lewis, J.K.; Bruender, N.A.; Bandarian, V.
QueE A radical SAM enzyme involved in the biosynthesis of 7-deazapurine containing natural products
Methods Enzymol.
606
95-118
2018
Bacillus subtilis (O31677), Bacillus subtilis 168 (O31677)
brenda
Grell, T.A.J.; Bell, B.N.; Nguyen, C.; Dowling, D.P.; Bruender, N.A.; Bandarian, V.; Drennan, C.L.
Crystal structure of AdoMet radical enzyme 7-carboxy-7-deazaguanine synthase from Escherichia coli suggests how modifications near [4Fe-4S] cluster engender flavodoxin specificity
Protein Sci.
28
202-215
2018
Escherichia coli
brenda