Information on EC 1.3.1.107 - sanguinarine reductase

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The expected taxonomic range for this enzyme is: Eschscholzia californica

EC NUMBER
COMMENTARY hide
1.3.1.107
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RECOMMENDED NAME
GeneOntology No.
sanguinarine reductase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
dihydrochelirubine + NAD(P)+ = chelirubine + NAD(P)H + H+
show the reaction diagram
dihydrosanguinarine + NAD(P)+ = sanguinarine + NAD(P)H + H+
show the reaction diagram
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
chelerythrine biosynthesis
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sanguinarine and macarpine biosynthesis
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SYSTEMATIC NAME
IUBMB Comments
dihydrosanguinarine:NAD(P)+ oxidoreductase
The enzyme, purified from the California poppy (Eschscholzia californica), is involved in detoxifying the phytoalexin sanguinarine produced by poppy itself (cf. EC 1.5.3.12, dihydrobenzophenanthridine oxidase), when it binds to the cell wall of the poppy cell. The reaction with NADPH is up to three times faster than that with NADH at low concentrations (<10 uM) of the dinucleotide. At higher concentrations the reaction with NADPH is inhibited but not that with NADH [1].
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
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RNAi-based silencing of sanguinarine reductase leads to displayed growth rates and morphology comparable to the wild type, but strains show either less or more of the slightly red color typical of benzophenanthridine producing cultures. Silenced strains give rise to mutants that either show a complete stop of elicitor-triggered alkaloid production or a burst of biosynthesis that severalfold surpasses the wild type level. The enzyme substrate, sanguinarine, inhibits phospholipase A2 at the plasma membrane, an initial component of the signal path towards expression of biosynthetic enzymes. The product, dihydrosanguinarine, inhibits enzymes of early biosynthesis, prior to reticuline formation. By tuning these steady states, sanguinarine reductase adjusts the capacity of alkaloid biosynthesis
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
cheleryhtrine + NAD(P)H + H+
dihydrocheleryhtrine + NAD(P)+
show the reaction diagram
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-
-
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dihydrochelirubine + NAD(P)+
chelirubine + NAD(P)H + H+
show the reaction diagram
key reaction of benzophenanthridine detoxification. Detoxifying the phytoalexin sanguinarine produced by Eschscholzia californica (California poppy) itself, when it binds to the cell wall of the poppy cell
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ir
dihydrochelirubine + NADP+
chelirubine + NADPH + H+
show the reaction diagram
dihydrochelirubine i.e. 5-methoxy-13-methyl-13,14-dihydro-2H,10H-[1,3]dioxolo[4,5-i][1,3]dioxolo[4',5':4,5]benzo[1,2-c]phenanthridinium. At alkaloid concentration below 0.1 mM, the reaction velocity is about threefold higher with NADPH than with NADH. Higher alkaloid concentrations cause the NADPH-dependent reduction to slow down, but not the NADH-driven reduction
chelirubine i.e. 5-methoxy-13-methyl-2H,10H-[1,3]dioxolo[4,5-i][1,3]dioxolo[4',5':4,5]benzo[1,2-c]phenanthridinium
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ir
dihydrosanguinarine + NAD(P)+
sanguinarine + NAD(P)H + H+
show the reaction diagram
key reaction of benzophenanthridine detoxification. Detoxifying the phytoalexin sanguinarine produced by Eschscholzia californica (California poppy) itself, when it binds to the cell wall of the poppy cell
-
-
ir
dihydrosanguinarine + NAD+
sanguinarine + NADH + H+
show the reaction diagram
dihydrosanguinarine i.e. 13-methyl-13,14-dihydro-2H,10H-[1,3]dioxolo[4,5-i][1,3]dioxolo[4',5':4,5]benzo[1,2-c]phenanthridine. At alkaloid concentration below 0.1 mM, the reaction velocity is about threefold higher with NADPH than with NADH. Higher alkaloid concentrations cause the NADPH-dependent reduction to slow down, but not the NADH-driven reduction
sanguinarine i.e. 13-methyl-2H,10H-[1,3]dioxolo[4,5-i][1,3]dioxolo[4',5':4,5]benzo[1,2-c]phenanthridinium
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ir
dihydrosanguinarine + NADP+
sanguinarine + NADPH + H+
show the reaction diagram
dihydrosanguinarine i.e. 13-methyl-13,14-dihydro-2H,10H-[1,3]dioxolo[4,5-i][1,3]dioxolo[4',5':4,5]benzo[1,2-c]phenanthridine. At alkaloid concentration below 0.1 mM, the reaction velocity is about threefold higher with NADPH than with NADH. Higher alkaloid concentrations cause the NADPH-dependent reduction to slow down, but not the NADH-driven reduction
sanguinarine i.e. 13-methyl-2H,10H-[1,3]dioxolo[4,5-i][1,3]dioxolo[4',5':4,5]benzo[1,2-c]phenanthridinium
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ir
sanguinarine + NADH + H+
dihydrosanguinarine + NAD+
show the reaction diagram
sanguinarine is converted 1.3times faster than chelerythrine. The reduction cannot be reversed by increasing the product concentrations, i.e. even a hundredfold excess of NAD(P)+ does not cause a detectable oxidation of added dihydrosanguinarine
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ir
sanguinarine + NADPH + H+
dihydrosanguinarine + NADP+
show the reaction diagram
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?
additional information
?
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catalytic mechanism is as follows: the alkanolamine form of sanguinarine is fixed in a binding pocket, mainly consisting of hydrophobic amino acids, by the conserved residue Ser153. Both dioxolane rings of the alkaloid are bound by a triad of H-bonds originating from Cys157 connected to Asp158 and His161 and by the side chain of Lys175. Electron transfer is initiated by attacking the C6 of sanguinarine with the hydride ion of NADPH and the OH group at C6 with a proton originating from Ser153. The anionic form of Ser is then stabilized by the NH3+ group of Lys175. Removal of OH- followed by water formation completes the reduction process
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
dihydrochelirubine + NAD(P)+
chelirubine + NAD(P)H + H+
show the reaction diagram
D5JWB3
key reaction of benzophenanthridine detoxification. Detoxifying the phytoalexin sanguinarine produced by Eschscholzia californica (California poppy) itself, when it binds to the cell wall of the poppy cell
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-
ir
dihydrosanguinarine + NAD(P)+
sanguinarine + NAD(P)H + H+
show the reaction diagram
D5JWB3
key reaction of benzophenanthridine detoxification. Detoxifying the phytoalexin sanguinarine produced by Eschscholzia californica (California poppy) itself, when it binds to the cell wall of the poppy cell
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ir
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NADH
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at alkaloid concentration below 0.1 mM, the reaction velocity is about threefold higher with NADPH than with NADH. Higher alkaloid concentrations cause the NADPH-dependent reduction to slow down, but not the NADH-driven reduction; below alkaloid substrate concentrations of 10 microM, the reaction velocity is about threefold higher with NADPH than with NADH and increases with the alkaloid concentration. Higher alkaloid concentrations cause the NADPH-dependent reduction to slow down, but not the NADH-driven reduction
NADPH
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at alkaloid concentration below 0.1 mM, the reaction velocity is about threefold higher with NADPH than with NADH. Higher alkaloid concentrations cause the NADPH-dependent reduction to slow down, but not the NADH-driven reduction; below alkaloid substrate concentrations of 10 microM, the reaction velocity is about threefold higher with NADPH than with NADH and increases with the alkaloid concentration. Higher alkaloid concentrations cause the NADPH-dependent reduction to slow down, but not the NADH-driven reduction
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0095
sanguinarine
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pH 7.5, 22°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
29430
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HPLC–mass spectrometry
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
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x * 29432, HPLC-MS
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
modeling of spatial conformation and catalytic site based on PDB entry 1XQ6
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in bacteria
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C157A
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15.1% of wild-type activity
D158N
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47.1% of wild-type activity
DELTA102-114
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2.5% of wild-type activity
F162P
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22% of wild-type activity
H161A
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15.6% of wild-type activity
M166L
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64.5% of wild-type activity
S153A
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4.0% of wild-type activity