Information on EC 4.2.1.115 - UDP-N-acetylglucosamine 4,6-dehydratase (configuration-inverting)

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The expected taxonomic range for this enzyme is: Bacteria

EC NUMBER
COMMENTARY
4.2.1.115
-
RECOMMENDED NAME
GeneOntology No.
UDP-N-acetylglucosamine 4,6-dehydratase (configuration-inverting)
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
UDP-N-acetyl-alpha-D-glucosamine = UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose + H2O
show the reaction diagram
-
-
-
-
UDP-N-acetyl-alpha-D-glucosamine = UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose + H2O
show the reaction diagram
Asp126, Lys127, and Tyr135 are the active site residues
-
UDP-N-acetyl-alpha-D-glucosamine = UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose + H2O
show the reaction diagram
reaction mechanism of WbpM
P72145
UDP-N-acetyl-alpha-D-glucosamine = UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose + H2O
show the reaction diagram
reaction mechanism, FlaA1 is a UDP-GlcNAc 4,6-dehydratase that additionally inverts the chirality at the C-5 position
-
UDP-N-acetyl-alpha-D-glucosamine = UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose + H2O
show the reaction diagram
catalytic mechanism of CapE, overview. Tyr164 does not act as the general base as it does in SDR enzymes displaying the SYK triad motif
Q7A2Y4
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Amino sugar and nucleotide sugar metabolism
-
-
CMP-pseudaminate biosynthesis
-
-
superpathway of UDP-N-acetylglucosamine-derived O-antigen building blocks biosynthesis
-
-
UDP-N-acetyl-beta-L-fucosamine biosynthesis
-
-
UDP-N-acetyl-beta-L-quinovosamine biosynthesis
-
-
SYSTEMATIC NAME
IUBMB Comments
UDP-N-acetylglucosamine hydro-lyase (inverting; UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose-forming)
Contains NADP+ as a cofactor. This is the first enzyme in the biosynthetic pathway of pseudaminic acid [3], a sialic-acid-like sugar that is unique to bacteria and is used by Helicobacter pylori to modify its flagellin. This enzyme plays a critical role in H. pylori's pathogenesis, being involved in the synthesis of both functional flagella and lipopolysaccharides [1,2]. It is completely inhibited by UDP-alpha-D-galactose. The reaction results in the chirality of the C-5 atom being inverted. It is thought that Lys-133 acts sequentially as a catalytic acid, protonating the C-6 hydroxy group and as a catalytic base, abstracting the C-5 proton, resulting in the elimination of water. This enzyme belongs to the short-chain dehydrogenase/reductase family of enzymes.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
FlaA1
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9076-60-2
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
strain B204, gene flaA1
-
-
Manually annotated by BRENDA team
Brachyspira hyodysenteriae B204
strain B204, gene flaA1
-
-
Manually annotated by BRENDA team
strain 11168
-
-
Manually annotated by BRENDA team
Campylobacter jejuni 11168
strain 11168
-
-
Manually annotated by BRENDA team
strain 26695
-
-
Manually annotated by BRENDA team
strain 26695, gene pseB
-
-
Manually annotated by BRENDA team
strain NCTC 11637; strain NCTC 11637, gene flaA1
UniProt
Manually annotated by BRENDA team
strain SS1; strain SS1, gene flaA1
UniProt
Manually annotated by BRENDA team
strains 26695 and J99
-
-
Manually annotated by BRENDA team
strain 26695, gene pseB
-
-
Manually annotated by BRENDA team
Helicobacter pylori NCTC 11637
strain NCTC 11637; strain NCTC 11637, gene flaA1
UniProt
Manually annotated by BRENDA team
strain SS1; strain SS1, gene flaA1
UniProt
Manually annotated by BRENDA team
strain PAO1, gene wbpM
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
Q7A2Y4
CapE belongs to a distinctive subfamily of SDR enzymes of pathogenic bacteria characterized by a singular catalytic triad displaying a Met residue (instead of the canonical Tyr residue) and a dynamic element known as the latch. Although CapE and FlaA1 afford the same product, the configuration of their active sites is different. Also, the latch region is absent in FlaA1
metabolism
Q7A2Y4
conversion of UDP-D-GlcNAc into UDP-L-FucNAc, an essential precursor of capsular polysaccharide requires three enzymes CapE, CapF, and CapG in Staphylococcus aureus. CapE yields the first intermediate of the sequential reactions catalyzed by these three enzymes
physiological function
Q7A2Y4
CapE is an essential enzyme for the synthesis of capsular polysaccharide of pathogenic strains of Staphylococcus aureus
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2 UDP-N-acetylglucosamine
UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-4-hexulose + UDP-2-acetamido-2,6-dideoxy-alpha-D-xylo-4-hexulose + 2 H2O
show the reaction diagram
-
the Cj1293 enzyme exhibits C6 dehydratase as well as C5 epimerase activity resulting in the production of both UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-4-hexulose and UDP-2-acetamido-2,6-dideoxy-alpha-D-xylo-4-hexulose. The enzyme is involved in biosynthesis of pseudaminic acid for glycomodification of the bacterial falgellins, overview
NMR analysis of reaction products, overview
-
?
2 UDP-N-acetylglucosamine
UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-4-hexulose + UDP-2-acetamido-2,6-dideoxy-alpha-D-xylo-4-hexulose + 2 H2O
show the reaction diagram
-
the HP0840 enzyme exhibits C6 dehydratase as well as C5 epimerase activity resulting in the production of both UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-4-hexulose and UDP-2-acetamido-2,6-dideoxy-alpha-D-xylo-4-hexulose. The enzyme is involved in biosynthesis of pseudaminic acid for glycomodification of the bacterial falgellins, overview
NMR analysis of reaction products, overview
-
?
2 UDP-N-acetylglucosamine
UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-4-hexulose + UDP-2-acetamido-2,6-dideoxy-alpha-D-xylo-4-hexulose + 2 H2O
show the reaction diagram
-
the HP0840 enzyme exhibits C6 dehydratase as well as C5 epimerase activity resulting in the production of both UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-4-hexulose and UDP-2-acetamido-2,6-dideoxy-alpha-D-xylo-4-hexulose. The enzyme is involved in biosynthesis of pseudaminic acid for glycomodification of the bacterial falgellins, overview
NMR analysis of reaction products, overview
-
?
UDP-6-deoxy-6-fluoro-GlcNAc
UDP-GlcNAc + HF
show the reaction diagram
-
elimination of fluoride from the substrate by the wild-type PseB, no activity by mutant enzymes K127A, D126N, and Y135F
-
-
?
UDP-GlcNAc
UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hexos-4-ulose + H2O
show the reaction diagram
-
the enzyme is involved in the pseudaminic acid biosynthesis, it is responsible for the biosynthesis of 6-deoxyhexose, the C-5'' epimerization of UDP-4-keto-6-deoxy-L-IdoNAc to UDP-4-keto-6-deoxy-GlcNAc is PseB-catalyzed, and isabout 50fold lower than the dehydratase activity
-
-
?
UDP-N-acetyl-alpha-D-glucosamine
UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose + H2O
show the reaction diagram
Q7A2Y4
CapE is a 5-inverting 4,6-dehydratase enzyme, but in the absence of downstream enzymes, CapE catalyzes an additional reaction (5-back-epimerization) affording a by-product UDP-xylo-sugar under thermodynamic control. The by-product structural analysis reveals a network of coordinated motions away from the active site governing the enzymatic activity of CapE. A second dynamic element (the latch) regulates the enzymatic chemoselectivity, second molecule of UDP-sugar is found at another binding pocket remote from the active site. The secondary binding site stabilizes the conformation of the latch and may play a role in the enzymatic regulation of CapE as observed in other enzymes. The by-product is anchored to the protein by non-covalent interactions through its UDP moiety
-
-
?
UDP-N-acetylglucosamine
UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose + H2O
show the reaction diagram
-
-
-
-
?
UDP-N-acetylglucosamine
UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose + H2O
show the reaction diagram
-
production of a precursor of pseudaminic acid, i.e. 5,7-diacetamido-3,5,7,9-tetradeoxy-L-glycero-alpha-L-manno-nonulosonic acid, required for flagellin glycosylation in Helicobacter pylori, analysis of all reaction steps in the pathway and related enzymes, overview
-
-
?
UDP-N-acetylglucosamine
UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose + H2O
show the reaction diagram
-
the enzyme catalyzes the first step in the biosynthetic pathway of a pseudaminic acid derivative, which is implicated in protein glycosylation
-
-
?
UDP-N-acetylglucosamine
UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose + H2O
show the reaction diagram
-
the enzyme is required for pseudaminic acid biosynthesis, which is required for O-linked flagellin glycosylation
-
-
?
UDP-N-acetylglucosamine
UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose + H2O
show the reaction diagram
P72145
WbpM is specific for UDP-GlcNAc
-
-
?
UDP-N-acetylglucosamine
UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose + H2O
show the reaction diagram
-
NMR reaction analysis, a possible three-step reaction mechanism that involves Lys133 functioning as both a catalytic acid and base
-
-
?
UDP-N-acetylglucosamine
UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose + H2O
show the reaction diagram
-
NMR reaction analysis, substrate binding at the active site, mapping of dynamic interactions of the enzyme with its ligand, molecular docking, overview
-
-
?
UDP-N-acetylglucosamine
UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose + H2O
show the reaction diagram
-
the enzyme catalyzes the stereospecific conversion of UDP-GlcNAc to Qui2NAc, i.e. 2-acetamido-2,6-dideoxy-D-glucose or N-acetylquinovosamine, via the formation of a 4-keto, 6-deoxy intermediate
-
-
?
UDP-N-acetylglucosamine
UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose + H2O
show the reaction diagram
P72145
WbpM is specific for UDP-GlcNAc. Although WbpM possesses an altered catalytic triad composed of SMK as opposed to SYK commonly found in other dehydratases, its catalysis is very efficient
-
-
?
UDP-N-acetylglucosamine
UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose + H2O
show the reaction diagram
-
production of a precursor of pseudaminic acid, i.e. 5,7-diacetamido-3,5,7,9-tetradeoxy-L-glycero-alpha-L-manno-nonulosonic acid, required for flagellin glycosylation in Helicobacter pylori, analysis of all reaction steps in the pathway and related enzymes, overview
-
-
?
2 UDP-N-acetylglucosamine
UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-4-hexulose + UDP-2-acetamido-2,6-dideoxy-alpha-D-xylo-4-hexulose + 2 H2O
show the reaction diagram
Campylobacter jejuni 11168
-
the Cj1293 enzyme exhibits C6 dehydratase as well as C5 epimerase activity resulting in the production of both UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-4-hexulose and UDP-2-acetamido-2,6-dideoxy-alpha-D-xylo-4-hexulose. The enzyme is involved in biosynthesis of pseudaminic acid for glycomodification of the bacterial falgellins, overview
NMR analysis of reaction products, overview
-
?
additional information
?
-
-
dependence of O-linked flagellin glycosylation on PseB, cross-talk between the Pse and alpha-D-QuiNAc4NAc, i.e. 2,4-diacetamido-2,4,6-trideoxy-a-d-Glc, pathways via PseB
-
-
-
additional information
?
-
Q6VYQ5, Q6VYQ6
the enzyme is involved in lipopolysaccharide biosynthesis, flagellum assembly, or protein glycosylation, and might play an important role in the pathogenesis of Helicobacter pylori. It is at the interface between several pathways that govern the expression of different virulence factors synthesizing sugar derivatives dedicated to the glycosylation of proteins which are involved in lipopolysaccharide and flagellum production with glycosylation regulating the activity of these proteins
-
-
-
additional information
?
-
Q6VYQ5, Q6VYQ6
the enzyme is involved in lipopolysaccharide biosynthesis, flagellum assembly, or protein glycosylation, and might play an important role in the pathogenesis of Helicobacter pylori. It is at the interface between several pathways that govern the expression of different virulence factors synthesizing sugar derivatives dedicated to the glycosylation of proteins which are involved in LPS and flagellum production with glycosylation regulating the activity of these proteins
-
-
-
additional information
?
-
-
the flagellar aminotransferases Cj1294 utilize only UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-4-hexulose as substrate producing UDP-4-amino-4,6-dideoxy-beta-L-AltNAc, a precursor in the Pse biosynthetic pathway
-
-
-
additional information
?
-
-
the flagellar aminotransferases HP0366 utilize only UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-4-hexulose as substrate producing UDP-4-amino-4,6-dideoxy-beta-L-AltNAc, a precursor in the Pse biosynthetic pathway
-
-
-
additional information
?
-
P72145
WbpM is essential for the biosynthesis of B-band lipopolysaccharide in many serotypes of Pseudomonas aeruginosa
-
-
-
additional information
?
-
-
FlaA1 is a bifunctional C6 dehydratase/C4 reductase specific for UDPGlcNAc. It converts UDP-GlcNAc into a UDP-4-keto-6-methyl-GlcNAc intermediate, which is stereospecifically reduced into UDP-QuiNAc
-
-
-
additional information
?
-
-
no activity with UDP-Glc, UDP-Gal, or UDP-GalNAc or with substrates of other known C6 dehydratases, i.e. GDP-mannose or dTDP-glucose, structure-function analysis, overview
-
-
-
additional information
?
-
P72145
no activity with UDP-Glc, UDP-GalNAc or UDP-Gal, and with substrates of other known C6 dehydratases such as GDP-mannose, dTDP-Glc and CDP-Glc. Structure-function analysis, although the membrane domains do not have any catalytic activity, they are important for the polymerization of high-molecular weight B-band lipopolysaccharide, overview
-
-
-
additional information
?
-
-
PseB catalyzes an additional C5 epimerization forming UDP-2-acetamido-2,6-dideoxy-alpha-D-xylo-hexos-4-ulose
-
-
-
additional information
?
-
-
the flagellar aminotransferases HP0366 utilize only UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-4-hexulose as substrate producing UDP-4-amino-4,6-dideoxy-beta-L-AltNAc, a precursor in the Pse biosynthetic pathway
-
-
-
additional information
?
-
Q6VYQ5
the enzyme is involved in lipopolysaccharide biosynthesis, flagellum assembly, or protein glycosylation, and might play an important role in the pathogenesis of Helicobacter pylori. It is at the interface between several pathways that govern the expression of different virulence factors synthesizing sugar derivatives dedicated to the glycosylation of proteins which are involved in LPS and flagellum production with glycosylation regulating the activity of these proteins
-
-
-
additional information
?
-
Campylobacter jejuni 11168
-
the flagellar aminotransferases Cj1294 utilize only UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-4-hexulose as substrate producing UDP-4-amino-4,6-dideoxy-beta-L-AltNAc, a precursor in the Pse biosynthetic pathway
-
-
-
additional information
?
-
Helicobacter pylori NCTC 11637
Q6VYQ6
the enzyme is involved in lipopolysaccharide biosynthesis, flagellum assembly, or protein glycosylation, and might play an important role in the pathogenesis of Helicobacter pylori. It is at the interface between several pathways that govern the expression of different virulence factors synthesizing sugar derivatives dedicated to the glycosylation of proteins which are involved in lipopolysaccharide and flagellum production with glycosylation regulating the activity of these proteins
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
2 UDP-N-acetylglucosamine
UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-4-hexulose + UDP-2-acetamido-2,6-dideoxy-alpha-D-xylo-4-hexulose + 2 H2O
show the reaction diagram
-
the Cj1293 enzyme exhibits C6 dehydratase as well as C5 epimerase activity resulting in the production of both UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-4-hexulose and UDP-2-acetamido-2,6-dideoxy-alpha-D-xylo-4-hexulose. The enzyme is involved in biosynthesis of pseudaminic acid for glycomodification of the bacterial falgellins, overview
-
-
?
2 UDP-N-acetylglucosamine
UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-4-hexulose + UDP-2-acetamido-2,6-dideoxy-alpha-D-xylo-4-hexulose + 2 H2O
show the reaction diagram
-
the HP0840 enzyme exhibits C6 dehydratase as well as C5 epimerase activity resulting in the production of both UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-4-hexulose and UDP-2-acetamido-2,6-dideoxy-alpha-D-xylo-4-hexulose. The enzyme is involved in biosynthesis of pseudaminic acid for glycomodification of the bacterial falgellins, overview
-
-
?
UDP-GlcNAc
UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hexos-4-ulose + H2O
show the reaction diagram
-
the enzyme is involved in the pseudaminic acid biosynthesis, it is responsible for the biosynthesis of 6-deoxyhexose
-
-
?
UDP-N-acetyl-alpha-D-glucosamine
UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose + H2O
show the reaction diagram
Q7A2Y4
-
-
-
?
UDP-N-acetylglucosamine
UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose + H2O
show the reaction diagram
-
-
-
-
?
UDP-N-acetylglucosamine
UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose + H2O
show the reaction diagram
-
production of a precursor of pseudaminic acid, i.e. 5,7-diacetamido-3,5,7,9-tetradeoxy-L-glycero-alpha-L-manno-nonulosonic acid, required for flagellin glycosylation in Helicobacter pylori, analysis of all reaction steps in the pathway and related enzymes, overview
-
-
?
UDP-N-acetylglucosamine
UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose + H2O
show the reaction diagram
-
the enzyme catalyzes the first step in the biosynthetic pathway of a pseudaminic acid derivative, which is implicated in protein glycosylation
-
-
?
UDP-N-acetylglucosamine
UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose + H2O
show the reaction diagram
-
the enzyme is required for pseudaminic acid biosynthesis, which is required for O-linked flagellin glycosylation
-
-
?
UDP-N-acetylglucosamine
UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose + H2O
show the reaction diagram
P72145
WbpM is specific for UDP-GlcNAc
-
-
?
UDP-N-acetylglucosamine
UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose + H2O
show the reaction diagram
-
production of a precursor of pseudaminic acid, i.e. 5,7-diacetamido-3,5,7,9-tetradeoxy-L-glycero-alpha-L-manno-nonulosonic acid, required for flagellin glycosylation in Helicobacter pylori, analysis of all reaction steps in the pathway and related enzymes, overview
-
-
?
2 UDP-N-acetylglucosamine
UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-4-hexulose + UDP-2-acetamido-2,6-dideoxy-alpha-D-xylo-4-hexulose + 2 H2O
show the reaction diagram
Campylobacter jejuni 11168
-
the Cj1293 enzyme exhibits C6 dehydratase as well as C5 epimerase activity resulting in the production of both UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-4-hexulose and UDP-2-acetamido-2,6-dideoxy-alpha-D-xylo-4-hexulose. The enzyme is involved in biosynthesis of pseudaminic acid for glycomodification of the bacterial falgellins, overview
-
-
?
additional information
?
-
-
dependence of O-linked flagellin glycosylation on PseB, cross-talk between the Pse and alpha-D-QuiNAc4NAc, i.e. 2,4-diacetamido-2,4,6-trideoxy-a-d-Glc, pathways via PseB
-
-
-
additional information
?
-
Q6VYQ5, Q6VYQ6
the enzyme is involved in lipopolysaccharide biosynthesis, flagellum assembly, or protein glycosylation, and might play an important role in the pathogenesis of Helicobacter pylori. It is at the interface between several pathways that govern the expression of different virulence factors synthesizing sugar derivatives dedicated to the glycosylation of proteins which are involved in lipopolysaccharide and flagellum production with glycosylation regulating the activity of these proteins
-
-
-
additional information
?
-
Q6VYQ5, Q6VYQ6
the enzyme is involved in lipopolysaccharide biosynthesis, flagellum assembly, or protein glycosylation, and might play an important role in the pathogenesis of Helicobacter pylori. It is at the interface between several pathways that govern the expression of different virulence factors synthesizing sugar derivatives dedicated to the glycosylation of proteins which are involved in LPS and flagellum production with glycosylation regulating the activity of these proteins
-
-
-
additional information
?
-
-
the flagellar aminotransferases Cj1294 utilize only UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-4-hexulose as substrate producing UDP-4-amino-4,6-dideoxy-beta-L-AltNAc, a precursor in the Pse biosynthetic pathway
-
-
-
additional information
?
-
-
the flagellar aminotransferases HP0366 utilize only UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-4-hexulose as substrate producing UDP-4-amino-4,6-dideoxy-beta-L-AltNAc, a precursor in the Pse biosynthetic pathway
-
-
-
additional information
?
-
P72145
WbpM is essential for the biosynthesis of B-band lipopolysaccharide in many serotypes of Pseudomonas aeruginosa
-
-
-
additional information
?
-
-
the flagellar aminotransferases HP0366 utilize only UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-4-hexulose as substrate producing UDP-4-amino-4,6-dideoxy-beta-L-AltNAc, a precursor in the Pse biosynthetic pathway
-
-
-
additional information
?
-
Q6VYQ5
the enzyme is involved in lipopolysaccharide biosynthesis, flagellum assembly, or protein glycosylation, and might play an important role in the pathogenesis of Helicobacter pylori. It is at the interface between several pathways that govern the expression of different virulence factors synthesizing sugar derivatives dedicated to the glycosylation of proteins which are involved in LPS and flagellum production with glycosylation regulating the activity of these proteins
-
-
-
additional information
?
-
Campylobacter jejuni 11168
-
the flagellar aminotransferases Cj1294 utilize only UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-4-hexulose as substrate producing UDP-4-amino-4,6-dideoxy-beta-L-AltNAc, a precursor in the Pse biosynthetic pathway
-
-
-
additional information
?
-
Helicobacter pylori NCTC 11637
Q6VYQ6
the enzyme is involved in lipopolysaccharide biosynthesis, flagellum assembly, or protein glycosylation, and might play an important role in the pathogenesis of Helicobacter pylori. It is at the interface between several pathways that govern the expression of different virulence factors synthesizing sugar derivatives dedicated to the glycosylation of proteins which are involved in lipopolysaccharide and flagellum production with glycosylation regulating the activity of these proteins
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NAD(P)+
-
dependent on, tightly bound
NADP+
-
NADP+/NADPH is tightly bound to FlaA1
NADP+
Q7A2Y4
binding and binding site structure, overview. Function of Tyr164 is related to its bulkiness in the relay mechanism
NADPH
Q7A2Y4
binding and binding site structure, overview. Function of Tyr164 is related to its bulkiness in the relay mechanism
additional information
-
the dehydratase does not require the addition of exogenous cofactor NAD(P)+
-
additional information
Q7A2Y4
the hexose ring occupies a non-catalytic conformation with respect to the coenzyme
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
CMP-pseudaminic acid
-
mapping of the dynamic interactions of the enzyme with the inhibitor, overview
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.151
UDP-N-acetylglucosamine
-
pH 7.0, 37C, mutant V266E
0.159
UDP-N-acetylglucosamine
-
pH 7.0, 37C, wild-type enzyme
0.251
UDP-N-acetylglucosamine
-
pH 10.0, 37C, mutant Y141M
0.494
UDP-N-acetylglucosamine
-
pH 7.0, 37C, mutant H86A
0.565
UDP-N-acetylglucosamine
-
pH 7.0, 37C, mutant Y141M
2.77
UDP-N-acetylglucosamine
P72145
pH 10.0, 30C, recombinant soluble truncated WbpM mutant His-S262
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.028
UDP-N-acetylglucosamine
-
pH 7.0, 37C, mutant Y141M
0.065
UDP-N-acetylglucosamine
-
pH 10.0, 37C, mutant Y141M
0.077
UDP-N-acetylglucosamine
-
pH 7.0, 37C, mutant H86A
0.095
UDP-N-acetylglucosamine
-
pH 7.0, 37C, wild-type enzyme
0.16
UDP-N-acetylglucosamine
-
pH 7.0, 37C, mutant V266E
2.8
UDP-N-acetylglucosamine
P72145
pH 10.0, 30C, recombinant soluble truncated WbpM mutant His-S262
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.000037
-
wild-type enzyme activity with UDP-6-deoxy-6-fluoro-GlcNAc for elimination of fluoride
0.23
-
wild-type enzyme activity with UDP-GlcNAc conversion to UDP-4-keto-6-deoxy-L-IdoNAc
additional information
-
-
additional information
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.2
-
assay at
7.4
-
assay at
8
Q7A2Y4
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
23 - 30
-
assay at
25 - 30
P72145
-
37
-
assay at
37
Q7A2Y4
assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
8.65
-
sequence calculation
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Brachyspira hyodysenteriae B204
-
-
-
-
Manually annotated by BRENDA team
Brachyspira hyodysenteriae B204
-
-
-
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Helicobacter pylori (strain ATCC 700392 / 26695)
Helicobacter pylori (strain ATCC 700392 / 26695)
Helicobacter pylori (strain ATCC 700392 / 26695)
Helicobacter pylori (strain ATCC 700392 / 26695)
Helicobacter pylori (strain ATCC 700392 / 26695)
Staphylococcus aureus (strain Mu50 / ATCC 700699)
Staphylococcus aureus (strain Mu50 / ATCC 700699)
Staphylococcus aureus (strain Mu50 / ATCC 700699)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
75000
-
about, recombinant His-tagged enzyme, gel filtration
692952
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
P72145
x * 63000, recombinant N-terminally His-tagged WbpM, SDS-PAGE, x * 64000, recombinant C-terminally His-tagged WbpM, SDS-PAGE, x * 60000, recombinant His-tagged truncated WbpM, SDS-PAGE
dimer
-
2 * 37400, recombinant His-tagged enzyme, SDS-PAGE
hexamer
-
the enzyme possesses a hexameric doughnut-shaped quaternary structure, crystal stucture analysis
additional information
-
FlaA1 is a short soluble protein that exhibits a typical SYK catalytic triad, structure-function analysis, overview
additional information
P72145
WbpM is anchored to the inner membrane via four N-terminal transmembrane domains, whereas the C-terminal catalytic domain resided in the cytoplasm, topological model of WbpM, overview
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
FlaA1-NADP+-UDP-GlcNAc and FlaA1-NADP+-UDPGlc ternary complexes, at room temperature by hanging-drop vapor diffusion in presence of NAD+, using as reservoir solution 10% v/v polyethylene glycol-200, 100 mM MES, pH 6.0, 5% v/w PEG 3000, and 4% acetone, and providing 10 mM excess of substrate, X-ray diffraction structure determination and analysis
-
purified enzyme in complex with by-product UDP-xylo-sugar from 10 mM Tris-HCl. pH 9.0, 30 mM NaCl, and 1 mM DTT, suitable crystals are soaked in mother liquor supplemented with 25% v/v glycerol and 0.5 mlM UDP-D-GlcNAc, X-ray diffraction structure determination and analysis at 1.88 A resolution. The structure of CapE is virtually identical to that of apo-CapE in complex with a substrate analogue
Q7A2Y4
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3)
-
recombinant His-tagged FlaA1 9.9fold from Escherichia coli strain BL21(DE3) to homogeneity by nickel chelation and cation exchange chromatography
-
recombinant N-terminally His-tagged and C-terminally His-tagged WbpMs from Escherichia coli by selective solubilization from the inner membrane by lauryl sarcosine and nickel chelation chromatography
P72145
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
gene flaA1, DNA and amino acid sequence determination and analysis
-
gene pseB, expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
-
gene flaA1, DNA and amino acid sequence determination, expression analysis; gene flaA1, DNA and amino acid sequence determination, expression analysis
Q6VYQ5, Q6VYQ6
gene flaA1, expression of the N-terminally His-tagged enzyme in Escherichia coli strain BL21(DE3), complementation of a Pseudomonas aeruginosa WbpM knockout by expression of His-tagged FlaA1
-
overexpression of wild-type N-terminally His-tagged and C-terminally His-tagged WbpMs, and mutant truncated WbpM in membranes of Escherichia coli, reaction yields are lower with C-terminally His-tagged than with N-terminally His-tagged recombinant enzyme
P72145
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D126N
-
site-directed mutagenesis, the mutant shows about 100fold lower activity with UDP-GlcNAc and with UDP-6-deoxy-6-fluoro-GlcNAc for HF elimination compared to the wild-type enzyme. Upon addition of UDP-4-keto-6-deoxy-GlcNAc to D126N the tightly bound NADPH is immediately oxidized
K127A
-
site-directed mutagenesis, the mutant shows about 100fold lower activity with UDP-GlcNAc and with UDP-6-deoxy-6-fluoro-GlcNAc for HF elimination compared to the wild-type enzyme. Upon addition of UDP-4-keto-6-deoxy-GlcNAc to K127A the tightly bound NADPH is immediately oxidized
Y135F
-
site-directed mutagenesis, the mutant shows about 100fold lower activity with UDP-GlcNAc and with UDP-6-deoxy-6-fluoro-GlcNAc for HF elimination compared to the wild-type enzyme, slow oxidation of NADPH upon addition of UDP-4-keto-6-deoxy-GlcNAc to Y135F
C103M
-
site-directed mutagenesis, the mutant is inactive, dimerization is prevented but the secondary structure is not significantly affected
C118M
-
site-directed mutagenesis, not recombinantly expressable mutant
D149K/K150A
-
site-directed mutagenesis, the mutant is inactive
D149K/K150D
-
site-directed mutagenesis, the mutant is inactive
D70A
-
site-directed mutagenesis, the mutant is inactive
D70N
-
site-directed mutagenesis, not recombinantly expressable mutant
G20A
-
site-directed mutagenesis, the mutant is inactive
H86A
-
site-directed mutagenesis, insoluble protein, the mutant shows reduced activity compared to the wild-type enzyme
H86F
-
site-directed mutagenesis, insoluble protein, the mutant is inactive
K133E
-
site-directed mutagenesis, inactive mutant
V266E
-
site-directed mutagenesis, the mutant shows increased activity compared to the wild-type enzyme
Y141F
-
site-directed mutagenesis, the mutant is inactive
F78W
Q7A2Y4
site-directed mutagenesis of a cofactor binding residue, the mutant shows similar activity compared to the wild-type enzyme
L122F
Q7A2Y4
site-directed mutagenesis of a cofactor binding residue, the mutant shows reduced activity compared to the wild-type enzyme
Y164A
Q7A2Y4
site-directed mutagenesis of a cofactor binding residue, the mutant shows highly reduced activity compared to the wild-type enzyme
Y164F
Q7A2Y4
site-directed mutagenesis of a cofactor binding residue, the mutant shows markedly reduced activity compared to the wild-type enzyme
additional information
-
disruption of flaA1 and flaB1 genes by replacement of internal fragments with chloramphenicol and/or kanamycin gene cassettes. Both mutations selectively abolish expression of the targeted gene without affecting synthesis of the other flagellar polypeptide. flaA1 and flaB1 mutant strains exhibit altered motility in vitro and are less efficient in movement through a liquid medium. Paradoxically, isogenic strains containing specifically disrupted flaA1 or flaB1 alleles are capable of assembling periplasmic flagella that are morphologically wild-type, phenotype, detailed overview
additional information
Brachyspira hyodysenteriae B204
-
disruption of flaA1 and flaB1 genes by replacement of internal fragments with chloramphenicol and/or kanamycin gene cassettes. Both mutations selectively abolish expression of the targeted gene without affecting synthesis of the other flagellar polypeptide. flaA1 and flaB1 mutant strains exhibit altered motility in vitro and are less efficient in movement through a liquid medium. Paradoxically, isogenic strains containing specifically disrupted flaA1 or flaB1 alleles are capable of assembling periplasmic flagella that are morphologically wild-type, phenotype, detailed overview
-
K133M
-
site-directed mutagenesis, inactive mutant
additional information
Q6VYQ5, Q6VYQ6
construction of flaA1 knockout mutant by gene disruption in strain NCTC 11637, the nonmotile mutant exhibits altered lipopolysaccharides, with loss of most O-antigen and core modification, and increased sensitivity to sodium dodecyl sulfate compared to wild-type bacteria. The flaA1 mutant produces flagellins but no flagellum. Phynotype, detailed overview
Y141M
-
site-directed mutagenesis of a FlaA1 catalytic triad mutant, the mutant shows slightly reduced activity compared to the wild-type enzyme
additional information
Helicobacter pylori NCTC 11637
-
construction of flaA1 knockout mutant by gene disruption in strain NCTC 11637, the nonmotile mutant exhibits altered lipopolysaccharides, with loss of most O-antigen and core modification, and increased sensitivity to sodium dodecyl sulfate compared to wild-type bacteria. The flaA1 mutant produces flagellins but no flagellum. Phynotype, detailed overview
-
additional information
P72145
construction of a soluble truncated form of WbpM, His-S262
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
-
PseB is a potential target for the development of antibiotics