Information on EC 1.1.98.3 - decaprenylphospho-beta-D-ribofuranose 2-dehydrogenase

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The expected taxonomic range for this enzyme is: Mycobacterium

EC NUMBER
COMMENTARY hide
1.1.98.3
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RECOMMENDED NAME
GeneOntology No.
decaprenylphospho-beta-D-ribofuranose 2-dehydrogenase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
trans,octacis-decaprenylphospho-beta-D-ribofuranose + FAD = trans,octacis-decaprenylphospho-beta-D-erythro-pentofuranosid-2-ulose + FADH2
show the reaction diagram
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
mycolyl-arabinogalactan-peptidoglycan complex biosynthesis
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SYSTEMATIC NAME
IUBMB Comments
trans,octacis-decaprenylphospho-beta-D-ribofuranose:FAD 2-oxidoreductase
The enzyme, isolated from the bacterium Mycobacterium smegmatis, is involved, along with EC 1.1.1.333, decaprenylphospho-D-erythro-pentofuranosid-2-ulose 2-reductase, in the epimerization of trans,octacis-decaprenylphospho-beta-D-ribofuranose to trans,octacis-decaprenylphospho-beta-D-arabinofuranose, the arabinosyl donor for the biosynthesis of mycobacterial cell wall arabinan polymers.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(2Z,6E)-farnesylphosphoryl-beta-D-ribofuranose + FAD
(2Z,6E)-farnesylphosphoryl-D-beta-D-erythro-pentofuranosid-2-ulose + FADH2
show the reaction diagram
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oxidation reaction calyzed by decaprenylphospho-beta-D-ribofuranose 2-oxidase DprE1
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?
trans,octacis-decaprenylphospho-beta-D-ribofuranose + FAD
trans,octacis-decaprenylphospho-beta-D-erythro-pentofuranosid-2-ulose + FADH2
show the reaction diagram
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oxidation reaction catalyzed by decaprenylphospho-beta-D-ribofuranose 2-oxidase DprE1
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?
additional information
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1-methyl-2,4,7-trinitroxanthone
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mutations C387S and C387G confer resistance to 1-methyl-2,4,7-trinitroxanthone
2-[(2S)-2-methyl-1,4-dioxa-8-azaspiro[4.5]dec-8-yl]-8-nitro-6-(trifluoromethyl)-4H-1,3-benzothiazin-4-one
3-nitro-N-[(1R)-1-phenylethyl]-5-(trifluoromethyl)benzamide
3-nitroso-N-[(1R)-1-phenylethyl]-5-(trifluoromethyl)benzamide
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benzothiazinone-derived inhibitor, binding includes a covalent link to conserved Cys387, and trifluoromethyl group is a second key determinant of interaction with the enzyme
N-(2-(4-methoxyphenoxy)ethyl)-3,5-dinitrobenzamide
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more than a ten-fold decrease in the number of colony-forming units is observed with both human and mouse primary cells at a N-(2-(4-methoxyphenoxy) ethyl)-3,5-dinitrobenzamide concentrations above 5 microM, compound is also highly active against multidrug-resistant and extensively drug-resistant clinical isolates. N-(2-(4-methoxyphenoxy)ethyl)-3,5-dinitrobenzamide shows a clear-cut effect on the synthesis of the arabinan domains of arabinogalactan and lipoarabinomannan, and inhibition of decaprenyl-phospho-arabinose formation in the treated extracts concurrent with the accumulation of decaprenylphospho-ribose. Target of the inhibitors is probably the heteromeric decaprenylphospho-ribose 29 epimerase encoded by the dprE1/dprE2 genes
N-(2-(benzyloxy)ethyl)-3,5-dinitrobenzamide
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more than a ten-fold decrease in the number of colony-forming units is observed with both human and mouse primary cells at a N-(2-(benzyloxy)ethyl)-3,5-dinitrobenzamide concentrations above 5 microM, compound is also highly active against multidrug-resistant and extensively drug-resistant clinical isolates. N-(2-(benzyloxy)ethyl)-3,5-dinitrobenzamide shows a clear-cut effect on the synthesis of the arabinan domains of arabinogalactan and lipoarabinomannan, and inhibition of decaprenyl-phospho-arabinose formation in the treated extracts concurrent with the accumulation of decaprenylphospho-ribose. Target of the inhibitors is probably the heteromeric decaprenylphospho-ribose 29 epimerase encoded by the dprE1/dprE2 genes
additional information
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benzothiazinone and dinitrobenzamide inhibitors target decaprenylphospho-beta-D-ribofuranose 2-oxidase DprE1. Several mutants showing high levels of dinitrobenzamide resistance, exhibit a mutation in residue Cys394 of DprE1
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PDB
SCOP
CATH
ORGANISM
UNIPROT
Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155)
Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155)
Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155)
Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
different crystal forms of ligand-free enzyme reveal considerable levels of structural flexibility of two surface loops that seem to govern accessibility of the active site. Structures of complexes with the benzothiazinone-derived nitroso derivative 3-nitroso-N-[(1R)-1-phenylethyl]-5-(trifluoromethyl)benzamide reveal that inhibitor binding includes a covalent link to conserved Cys387, and reveal a trifluoromethyl group as a second key determinant of interaction with the enzyme. A noncovalent complex is formed between the enzyme and 3-nitro-N-[(1R)-1-phenylethyl]-5-(trifluoromethyl)benzamide, which is structurally identical to 3-nitroso-N-[(1R)-1-phenylethyl]-5-(trifluoromethyl)benzamide except for an inert nitro group replacing the reactive nitroso group. Binding of benzothiazinone-class inhibitors to the enzyme is not strictly dependent on formation of the covalent link to Cys387
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C394G
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benzothiazinone-resistant mutant, reduces benzothiazinones to inert metabolites while avoiding covalent inactivation
C394S
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benzothiazinone-resistant mutant, reduces benzothiazinones to inert metabolites while avoiding covalent inactivation
C387G
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mutation confers resistance to 1-methyl-2,4,7-trinitroxanthone and to 3-nitro-N-[(1R)-1-phenylethyl]-5-(trifluoromethyl)benzamide
C387S
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mutation confers resistance to 1-methyl-2,4,7-trinitroxanthone and to 3-nitro-N-[(1R)-1-phenylethyl]-5-(trifluoromethyl)benzamide
C387G
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mutation confers resistance to 1-methyl-2,4,7-trinitroxanthone and to 3-nitro-N-[(1R)-1-phenylethyl]-5-(trifluoromethyl)benzamide
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C387S
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mutation confers resistance to 1-methyl-2,4,7-trinitroxanthone and to 3-nitro-N-[(1R)-1-phenylethyl]-5-(trifluoromethyl)benzamide
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additional information
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isolation of mutant strains resistant to dinitrobenzamides. All mutants show cross-resistance to benzothiazinones and dinitrobenzamides, and all the mutant strains with a higher level of resistance to dinitrobenzamides have a substitution C394G of MSMEG_6382 gene encoding decaprenylphospho-?-D-ribofuranose 2-oxidase
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis