Information on EC 1.1.1.305 - UDP-glucuronic acid dehydrogenase (UDP-4-keto-hexauronic acid decarboxylating):
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The lowest common taxonomy group for this enzyme is: Escherichia coli

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EC NUMBERCOMMENTARY
1.1.1.305-

RECOMMENDED NAMEGeneOntology No.
UDP-glucuronic acid dehydrogenase (UDP-4-keto-hexauronic acid decarboxylating)-

REACTIONREACTION DIAGRAMCOMMENTARYORGANISM UNIPROT ACCESSION NO.LITERATURE
UDP-glucuronate + NAD+ = UDP-beta-L-threo-pentapyranos-4-ulose + CO2 + NADH + H+
show the reaction diagram		----
UDP-glucuronate + NAD+ = UDP-beta-L-threo-pentapyranos-4-ulose + CO2 + NADH + H+
show the reaction diagram		-Escherichia coli-698730

REACTION TYPEORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATURE
No entries in this field

PATHWAYKEGG LinkMetaCyc Link
polymyxin resistance-PWY0-1338

SYSTEMATIC NAMEIUBMB Comments
UDP-glucuronate:NAD+ oxidoreductase (decarboxylating)The activity is part of a bifunctional enzyme also performing the reaction of EC 2.1.2.13 (UDP-4-amino-4-deoxy-L-arabinose formyltransferase).

SYNONYMSORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATURE
ArnA dehydrogenaseEscherichia coli--698730, 701248
ArnADHEscherichia coli-ArnA is a bifunctional enzyme, ArnADH protein consists of the C-terminal 345 residues of ArnA, starting at Thr-316 converted to an initiating methionine698730
ArnADHEscherichia coli--701248
UDP-GlcUA dehydrogenaseEscherichia coli--698730

CAS REGISTRY NUMBERCOMMENTARY
No entries in this field

ORGANISMCOMMENTARYLITERATURESEQUENCE CODESEQUENCE DB SOURCE
Escherichia coli-696203, 698732, 701248P77398UniprotManually annotated by BRENDA team
Escherichia coli-698730--Manually annotated by BRENDA team
Escherichia colipolymyxin-resistant mutant698723P77398UniprotManually annotated by BRENDA team

GENERAL INFORMATIONORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATURE
No entries in this field

SUBSTRATEPRODUCT                      REACTION DIAGRAMORGANISM UNIPROT ACCESSION NO. COMMENTARY/
Substrate		 LITERATURE/
Substrate		 COMMENTARY/
Product		 LITERATURE/
Product		 Reversibility
r=reversible
ir=irreversible
?=not specified
UDP-glucuronate + NAD+UDP-beta-L-threo-pentapyranos-4-ulose + CO2 + NADH + H+
show the reaction diagram		Escherichia coliP77398-698723--?
UDP-glucuronate + NAD+UDP-beta-L-threo-pentapyranos-4-ulose + CO2 + NADH + H+
show the reaction diagram		Escherichia coli-ArnA is a bi-functional enzyme, the oxidative decarboxylation of UDP-glucuronic acid is catalyzed by the 345-residue C-terminal domain of ArnA. The 304-residue N-terminal domain catalyzes the N-10-formyltetrahydrofolate-dependent formylation of the 4''-amine of UDP-L-4-amino-4-deoxy-L-arabinose, generating the sugar nucleotide, uridine 5'-diphospho-beta-(4-deoxy-4-formamido-L-arabinose). The two domains of ArnA are expressed independently as active proteins in Escherichia coli. Both are required for maintenance of polymyxin resistance and 4-amino-4-deoxy-L-arabinose modification of lipid A. only the formylated sugar nucleotide is converted in vitro to an undecaprenyl phosphate-linked form by the enzyme ArnC698730--?
UDP-glucuronate + NAD+UDP-beta-L-threo-pentapyranos-4-ulose + CO2 + NADH + H+
show the reaction diagram		Escherichia coliP77398ArnA is a key enzyme in the lipid A modification pathway, and its deletion abolishes both the Ara4N-lipid A modification and polymyxin resistance. ArnA is a bifunctional enzyme. It can catalyze the NAD+-dependent decarboxylation of UDP-glucuronic acid to UDP-4-keto-arabinose and the N-10-formyltetrahydrofolatedependent formylation of UDP-4-amino-4-deoxy-L-arabinose696203--?
UDP-glucuronate + NAD+UDP-beta-L-threo-pentapyranos-4-ulose + CO2 + NADH + H+
show the reaction diagram		Escherichia coli-modification of the lipid A moiety of lipopolysaccharide by the addition of the sugar 4-amino-4-deoxy-L-arabinose is a strategy adopted by pathogenic Gram-negative bacteria to evade cationic antimicrobial peptides produced by the innate immune system. The bifunctional enzyme ArnA is required for 4-amino-4-deoxy-L-arabinose biosynthesis and catalyzes the NAD+-dependent oxidative decarboxylation of UDP-glucuronic acid to generate a UDP-4'-keto-pentose sugar and also catalyzes transfer of a formyl group from N-10-formyltetrahydrofolate to the 4'-amine of UDP-4-amino-4-deoxy-L-arabinose698732--?
UDP-glucuronate + NAD+UDP-beta-L-threo-pentapyranos-4-ulose + CO2 + NADH + H+
show the reaction diagram		Escherichia coli-the modification of lipid A with 4-amino-4-deoxy-L-arabinose allows gram-negative bacteria to resist the antimicrobial activity of cationic antimicrobial peptides and antibiotics such as polymyxin. ArnA is the first enzyme specific to the lipid A-Ara4N pathway. It contains two functionally and physically separable domains: a dehydrogenase domain (ArnA_DH) catalyzing the NAD+-dependent oxidative decarboxylation of UDP-glucuronic acid, and a transformylase domain that formylates UDP-4-amino-4-deoxy-L-arabinose701248--?
UDP-glucuronate + NAD+UDP-beta-L-threo-pentapyranos-4-ulose + CO2 + NADH + H+
show the reaction diagram		Escherichia coli-ArnA is a bi-functional enzyme. The oxidative decarboxylation of UDP-glucuronic acid is catalyzed by the 345-residue C-terminal domain of ArnA. The 304-residue N-terminal domain catalyzes the N-10-formyltetrahydrofolate-dependent formylation of the 4''-amine of UDP-4-amino-4-deoxy-L-arabinose, generating the sugar nucleotide, uridine 5'-diphospho-beta-(4-deoxy-4-formamido-L-arabinose)698730--?
UDP-glucuronate + NAD+UDP-beta-L-threo-pentapyranos-4-ulose + CO2 + NADH + H+
show the reaction diagram		Escherichia coliP77398ArnA is a bifunctional enzyme. It can catalyze the NAD+-dependent decarboxylation of UDP-glucuronic acid to UDP-4-keto-arabinose and the N-10-formyltetrahydrofolatedependent formylation of UDP-4-amino-4-deoxy-L-arabinose. The NAD+-dependent decarboxylating activity is contained in the 360 amino acid C-terminal domain of ArnA. This domain is separable from the N-terminal fragment, and its activity is identical to that of the full-length enzyme. T432, Y463, K467, R619, and S433 are involved in the mechanism of NAD+-dependent oxidation of the 4''-OH of the UDP-glucuronic acid and decarboxylation of the UDP-4-keto-glucuronic acid intermediate696203--?
UDP-glucuronate + NAD+UDP-beta-L-threo-pentapyranos-4-ulose + CO2 + NADH + H+
show the reaction diagram		Escherichia coli-modification of the lipid A moiety of lipopolysaccharide by the addition of the sugar 4-amino-4-deoxy-L-arabinose is a strategy adopted by pathogenic Gram-negative bacteria to evade cationic antimicrobial peptides produced by the innate immune system. The bifunctional enzyme ArnA is required for 4-amino-4-deoxy-L-arabinose biosynthesis and catalyzes the NAD+-dependent oxidative decarboxylation of UDP-glucuronic acid to generate a UDP-4'-keto-pentose sugar and also catalyzes transfer of a formyl group from N-10-formyltetrahydrofolate to the 4'-amine of UDP-4-amino-4-deoxy-L-arabinose. Residues Ser433 and Glu434 of the decarboxylase domain are required for the oxidative decarboxylation of UDP-glucuronate. Decarboxylase domain catalyzes both hydride abstraction (oxidation) from the C-4' position and the subsequent decarboxylation698732--?
UDP-glucuronate + NAD+UDP-beta-L-threo-pentapyranos-4-ulose + CO2 + NADH + H+
show the reaction diagram		Escherichia coli-ordered mechanism of substrate binding and product release is proposed. R619 functions as a general acid in catalysis701248--?

NATURAL SUBSTRATESNATURAL PRODUCTSREACTION DIAGRAMORGANISM UNIPROT ACCESSION NO.COMMENTARY SUBSTRATELITERATURE
(Substrate)		COMMENTARY PRODUCTLITERATURE
(Product)
UDP-glucuronate + NAD+UDP-beta-L-threo-pentapyranos-4-ulose + CO2 + NADH + H+
show the reaction diagram		Escherichia coliP77398-698723--
UDP-glucuronate + NAD+UDP-beta-L-threo-pentapyranos-4-ulose + CO2 + NADH + H+
show the reaction diagram		Escherichia coli-ArnA is a bi-functional enzyme, the oxidative decarboxylation of UDP-glucuronic acid is catalyzed by the 345-residue C-terminal domain of ArnA. The 304-residue N-terminal domain catalyzes the N-10-formyltetrahydrofolate-dependent formylation of the 4''-amine of UDP-L-4-amino-4-deoxy-L-arabinose, generating the sugar nucleotide, uridine 5'-diphospho-beta-(4-deoxy-4-formamido-L-arabinose). The two domains of ArnA are expressed independently as active proteins in Escherichia coli. Both are required for maintenance of polymyxin resistance and 4-amino-4-deoxy-L-arabinose modification of lipid A. only the formylated sugar nucleotide is converted in vitro to an undecaprenyl phosphate-linked form by the enzyme ArnC698730--
UDP-glucuronate + NAD+UDP-beta-L-threo-pentapyranos-4-ulose + CO2 + NADH + H+
show the reaction diagram		Escherichia coliP77398ArnA is a key enzyme in the lipid A modification pathway, and its deletion abolishes both the Ara4N-lipid A modification and polymyxin resistance. ArnA is a bifunctional enzyme. It can catalyze the NAD+-dependent decarboxylation of UDP-glucuronic acid to UDP-4-keto-arabinose and the N-10-formyltetrahydrofolatedependent formylation of UDP-4-amino-4-deoxy-L-arabinose696203--
UDP-glucuronate + NAD+UDP-beta-L-threo-pentapyranos-4-ulose + CO2 + NADH + H+
show the reaction diagram		Escherichia coli-modification of the lipid A moiety of lipopolysaccharide by the addition of the sugar 4-amino-4-deoxy-L-arabinose is a strategy adopted by pathogenic Gram-negative bacteria to evade cationic antimicrobial peptides produced by the innate immune system. The bifunctional enzyme ArnA is required for 4-amino-4-deoxy-L-arabinose biosynthesis and catalyzes the NAD+-dependent oxidative decarboxylation of UDP-glucuronic acid to generate a UDP-4'-keto-pentose sugar and also catalyzes transfer of a formyl group from N-10-formyltetrahydrofolate to the 4'-amine of UDP-4-amino-4-deoxy-L-arabinose698732--
UDP-glucuronate + NAD+UDP-beta-L-threo-pentapyranos-4-ulose + CO2 + NADH + H+
show the reaction diagram		Escherichia coli-the modification of lipid A with 4-amino-4-deoxy-L-arabinose allows gram-negative bacteria to resist the antimicrobial activity of cationic antimicrobial peptides and antibiotics such as polymyxin. ArnA is the first enzyme specific to the lipid A-Ara4N pathway. It contains two functionally and physically separable domains: a dehydrogenase domain (ArnA_DH) catalyzing the NAD+-dependent oxidative decarboxylation of UDP-glucuronic acid, and a transformylase domain that formylates UDP-4-amino-4-deoxy-L-arabinose701248--

COFACTORORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATUREIMAGE
NAD+Escherichia coli--696203, 698730, 698732, 701248 2D-image

METALS and IONS ORGANISM UNIPROT ACCESSION NO.COMMENTARY LITERATURE
No entries in this field

INHIBITORSORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE IMAGE
No entries in this field

ACTIVATING COMPOUNDORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE IMAGE
No entries in this field

KM VALUE [mM]KM VALUE [mM] MaximumSUBSTRATEORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE IMAGE
0.57-NAD+Escherichia coli-pH 8.0, 37°C, C-terminal domain of ArnA696203 2D-image
0.76-NAD+Escherichia coli-pH 8.0, 37°C, full-length enzyme696203 2D-image
1.3-NAD+Escherichia coli-pH 7.5, 30°C, ArnA decarboxylase domain698732 2D-image
1.4-NAD+Escherichia coli-pH 7.5, 30°C, S433A decarboxylase mutant698732 2D-image
1.6-NAD+Escherichia coli-pH 7.5, 30°C, E434A decarboxylase mutant, E434Q decarboxylase mutant698732 2D-image
0.054-UDP-glucuronateEscherichia coli-pH 8.0, 37°C, C-terminal domain of ArnA696203 2D-image
0.086-UDP-glucuronateEscherichia coli-pH 8.0, 37°C, full-length enzyme696203 2D-image
0.2-UDP-glucuronateEscherichia coli-pH 7.5, 30°C, S433A decarboxylase mutant698732 2D-image
0.4-UDP-glucuronateEscherichia coli-pH 7.5, 30°C, E434A decarboxylase mutant698732 2D-image
0.7-UDP-glucuronateEscherichia coli-pH 7.5, 30°C, ArnA decarboxylase domain698732 2D-image

TURNOVER NUMBER [1/s] TURNOVER NUMBER MAXIMUM[1/s] SUBSTRATEORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE IMAGE
No entries in this field

kcat/KM VALUE [1/mMs-1]kcat/KM VALUE [1/mMs-1] MaximumSUBSTRATEORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE IMAGE
No entries in this field

Ki VALUE [mM]Ki VALUE [mM] MaximumINHIBITORORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE IMAGE
No entries in this field

IC50 VALUE [mM]IC50 VALUE [mM] MaximumINHIBITORORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE IMAGE
No entries in this field

SPECIFIC ACTIVITY [µmol/min/mg] SPECIFIC ACTIVITY MAXIMUM ORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE
No entries in this field

pH OPTIMUMpH MAXIMUMORGANISM UNIPROT ACCESSION NO. COMMENTARYLITERATURE
7.5-Escherichia coli-assay at698730, 698732
8-Escherichia coli-assay at696203

pH RANGEpH RANGE MAXIMUMORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATURE
No entries in this field

TEMPERATURE OPTIMUMTEMPERATURE OPTIMUM MAXIMUMORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATURE
30-Escherichia coli-assay at698730, 698732
37-Escherichia coli-assay at696203

TEMPERATURE RANGE TEMPERATURE MAXIMUM ORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE
No entries in this field

pI VALUEpI VALUE MAXIMUMORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATURE
No entries in this field

SOURCE TISSUE ORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE SOURCE
No entries in this field

LOCALIZATION ORGANISM UNIPROT ACCESSION NO. COMMENTARY GeneOntology No. LITERATURE SOURCE
No entries in this field

PDBSCOPCATHORGANISM
No entries in this field

MOLECULAR WEIGHT MOLECULAR WEIGHT MAXIMUM ORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE
No entries in this field

SUBUNITS ORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE
No entries in this field

POSTTRANSLATIONAL MODIFICATION ORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE
No entries in this field

Crystallization/COMMENTARY ORGANISM UNIPROT ACCESSION NO. LITERATURE
crystal structure of the ArnA decarboxylase domainEscherichia coli-696203
crystallization of native and Se-Met decarboxylase protein. Good quality crystals are obtained with a precipitant solution of 3.2 M NaCl, 0.1 M Bistris, pH 5.2, using a drop containing 0.004 ml of protein and 0.004 ml of precipitant equilibrated against a reservoir of 0.1 ml of precipitant. Space group as P4(1)3(2), with cell dimensions a = b = c = 149.4 A, beta = gamma = 90°Escherichia coli-698732
hanging drop vapor diffusion method, crystal structure of the full-length bifunctional ArnA with UDP-glucuronic acid and ATP bound to the dehydrogenase domain. Binding of UDP-glucuronic acid triggers a 17 A conformational change in ArnA_DH that opens the NAD+ binding site while trapping UDP-glucuronic acidEscherichia coli-701248

pH STABILITYpH STABILITY MAXIMUM ORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE
No entries in this field

TEMPERATURE STABILITYTEMPERATURE STABILITY MAXIMUM ORGANISM UNIPROT ACCESSION NO. COMMENTARYLITERATURE
No entries in this field

GENERAL STABILITYORGANISM UNIPROT ACCESSION NO.LITERATURE
No entries in this field

ORGANIC SOLVENT ORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE
No entries in this field

OXIDATION STABILITY ORGANISM UNIPROT ACCESSION NO. LITERATURE
No entries in this field

STORAGE STABILITY ORGANISM UNIPROT ACCESSION NO. LITERATURE
No entries in this field

Purification/COMMENTARY ORGANISM UNIPROT ACCESSION NO. LITERATURE
-Escherichia coli-701248
recombinantEscherichia coli-698730

Cloned/COMMENTARY ORGANISM UNIPROT ACCESSION NO. LITERATURE
-Escherichia coli-701248
overexpression of ArnA as a hexahistidine fusion protein, cloning and expression the separate domains in pET28b and pWSK29Escherichia coli-698730
overexpression of native and selenomethionine decarboxylase and formyltransferase domains of ArnAEscherichia coli-698732

EXPRESSION ORGANISM UNIPROT ACCESSION NO. LITERATURE
No entries in this field

ENGINEERINGORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATURE
E434QEscherichia coli-mutant is inactive, suggesting that chemical rather than steric properties of this residue are crucial in the decarboxylation reaction698732
R610MEscherichia coli-activity is 800fold lower than wild-type activity701248
R619EEscherichia coli-no activity701248
R619YEscherichia coli-no activity701248
S433AEscherichia coli-activity is 30fold lower than wild-type activity701248
S433TEscherichia coli-no activity701248

Renatured/COMMENTARYORGANISM UNIPROT ACCESSION NO.LITERATURE
No entries in this field

APPLICATIONORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATURE
medicineEscherichia coli-modification of the lipid A moiety of lipopolysaccharide by the addition of the sugar 4-amino-4-deoxy-L-arabinose is a strategy adopted by pathogenic Gram-negative bacteria to evade cationic antimicrobial peptides produced by the innate immune system. L-Ara4N biosynthesis is therefore a potential anti-infective target698732

REF. AUTHORS TITLE JOURNAL VOL. PAGES YEAR ORGANISMLINK TO PUBMEDSOURCE
696203Gatzeva-Topalova, P.Z.; May, A.P.; Sousa, M.C.Crystal structure of Escherichia coli ArnA (PmrI) decarboxylase domain. A key enzyme for lipid A modification with 4-amino-4-deoxy-L-arabinose and polymyxin resistanceBiochemistry4313370-133792005Escherichia coli PubMed
698723Breazeale, S.D.; Ribeiro, A.A.; Raetz, C.R.Oxidative decarboxylation of UDP-glucuronic acid in extracts of polymyxin-resistant Escherichia coli. Origin of lipid a species modified with 4-amino-4-deoxy-L-arabinoseJ. Biol. Chem.2772886-28962001Escherichia coli PubMed
698730Breazeale, S.D.; Ribeiro, A.A.; McClerren, A.L.; Raetz, C.R.A formyltransferase required for polymyxin resistance in Escherichia coli and the modification of lipid A with 4-Amino-4-deoxy-L-arabinose. Identification and function oF UDP-4-deoxy-4-formamido-L-arabinoseJ. Biol. Chem.28014154-141672005Escherichia coli PubMed
698732Williams, G.J.; Breazeale, S.D.; Raetz. C.R.; Naismith. J.H.Structure and function of both domains of ArnA, a dual function decarboxylase and a formyltransferase, involved in 4-amino-4-deoxy-L-arabinose biosynthesisJ. Biol. Chem.28023000-230082005Escherichia coli PubMed
701248Gatzeva-Topalova, P.Z.; May, A.P.; Sousa, M.C.Structure and mechanism of ArnA: conformational change implies ordered dehydrogenase mechanism in key enzyme for polymyxin resistance.Structure13929-9422005Escherichia coli PubMed

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