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Information on EC 5.1.3.14 - UDP-N-acetylglucosamine 2-epimerase (non-hydrolysing)
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5.1.3.14 UDP-N-acetylglucosamine 2-epimerase (non-hydrolysing)IUBMB Comments
This bacterial enzyme catalyses the reversible interconversion of UDP-GlcNAc and UDP-ManNAc. The latter is used in a variety of bacterial polysaccharide biosyntheses.
cf. EC 3.2.1.183, UDP-N-acetylglucosamine 2-epimerase (hydrolysing).
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Word Map
- 5.1.3.14
-
sialic
- myopathy
- hereditary
- vacuoles
-
rimmed
-
sialylation
-
quadriceps
- sialuria
- glycoconjugates
-
hyposialylation
- udp-n-acetylmannosamine
- neu5ac
-
cmp-n-acetylneuraminic
-
nonaka
-
inclusion-body
-
cmp-sialic
-
udp-mannac
- cmp-neu5ac
- synthesis
- biotechnology
- medicine
- drug development
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
bas5048, bas5117, Bs-epimerase, Epimerase, uridine diphosphoacetylglucosamine 2-, GNE, GNE/MNK, GNE1, GNE2, GneY, GneZ, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Bs-epimerase
Epimerase, uridine diphosphoacetylglucosamine 2-
-
-
-
-
GNE
GNE/MNK
GNE1
NeuC protein
non-hydrolyzing UDP-GlcNAc 2-epimerase
non-hydrolyzing UDP-N-acetylglucosamine 2-epimerase
non-hydrolyzing uridine 5'-diphosphate-N-acetylglucosamine 2-epimerase
SacA
UDP-GlcNAc 2'-epimerase
UDP-GlcNAc 2-epimerase
UDP-GlcNAc 2-epimerase/ManNAc kinase
UDP-GlcNAc-2-epimerase
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-
-
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UDP-N-acetylglucosamine 2'-epimerase
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UDP-N-acetylglucosamine 2-epimerase
UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase
uridine diphosphate N-acetylglucosamine 2-epimerase
Uridine diphosphate-N-acetylglucosamine-2'-epimerase
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-
-
-
Uridine diphospho-N-acetylglucosamine 2'-epimerase
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-
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Uridine diphosphoacetylglucosamine 2'-epimerase
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-
-
-
additional information
non-hydrolyzing UDP-GlcNAc 2-epimerase
Neisseria meningitidis serogroup A / serotype 4A
-
non-hydrolyzing UDP-GlcNAc 2-epimerase
Neisseria meningitidis serogroup A / serotype 4A Z2491
-
-
non-hydrolyzing UDP-N-acetylglucosamine 2-epimerase
Neisseria meningitidis serogroup A / serotype 4A
-
non-hydrolyzing UDP-N-acetylglucosamine 2-epimerase
Neisseria meningitidis serogroup A / serotype 4A Z2491
-
-
non-hydrolyzing uridine 5'-diphosphate-N-acetylglucosamine 2-epimerase
Neisseria meningitidis serogroup A / serotype 4A
-
non-hydrolyzing uridine 5'-diphosphate-N-acetylglucosamine 2-epimerase
Neisseria meningitidis serogroup A / serotype 4A Z2491
-
-
UDP-GlcNAc 2'-epimerase
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-
-
-
UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
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-
UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
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bifunctional enzyme
UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
-
bifunctional
UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
-
bifunctional enzyme
additional information
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bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
additional information
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bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/ManNAc kinase
additional information
-
bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
UDP-N-acetyl-alpha-D-glucosamine = UDP-N-acetyl-alpha-D-mannosamine
-
-
-
-
UDP-N-acetyl-alpha-D-glucosamine = UDP-N-acetyl-alpha-D-mannosamine
products: UDP + N-acetyl-D-mannosamine; UDP-N-acetyl-D-mannosamine is not an intermediate
-
UDP-N-acetyl-alpha-D-glucosamine = UDP-N-acetyl-alpha-D-mannosamine
products: UDP + N-acetyl-D-mannosamine
-
UDP-N-acetyl-alpha-D-glucosamine = UDP-N-acetyl-alpha-D-mannosamine
ordered mechanism, where UDP is the first product released followed by irreversible formation of N-acetyl-mannosamine. A two step mechanism is proposed which involves the elimination of UDP from UDP-N-acetylglucosamine to give a 2-acetamidoglucal intermediate which is subsequently converted to N-acetylmannosamine; products: UDP + N-acetyl-D-mannosamine
-
UDP-N-acetyl-alpha-D-glucosamine = UDP-N-acetyl-alpha-D-mannosamine
during epimerization, tritium from tritium-enriched water is incorporated into both UDP-N-acetyl-D-glucosamine and UDP-N-acetyl-D-mannosamine
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UDP-N-acetyl-alpha-D-glucosamine = UDP-N-acetyl-alpha-D-mannosamine
the mechanism involves a trans-elimination of monoprotic UDP to form 2-acetamidoglucal. Followed by a syn-addition, in the direction of UDP-N-acetyl-D-mannosamine formation
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UDP-N-acetyl-alpha-D-glucosamine = UDP-N-acetyl-alpha-D-mannosamine
mechanism proceeds via cleavage of the anomeric C-O bond, with 2-acetamidoglucal and UDP as enzyme-bound intermediates. It is likely that E1-eliminations via oxocarbenium intermediates are involved in the reaction
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UDP-N-acetyl-alpha-D-glucosamine = UDP-N-acetyl-alpha-D-mannosamine
2-epimerase-catalyzed elimination and readdition of UDP to the glycal intermediate may proceed through a transition state with significant oxocarbenium ion-like character
UDP-N-acetyl-alpha-D-glucosamine = UDP-N-acetyl-alpha-D-mannosamine
2-epimerase-catalyzed elimination and readdition of UDP to the glycal intermediate may proceed through a transition state with significant oxocarbenium ion-like character
Q9REV4
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
epimerization
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-
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PATHWAY SOURCE
PATHWAYS
MetaCyc
poly(3-O-beta-D-glucopyranosyl-N-acetylgalactosamine 1-phosphate) wall teichoic acid biosynthesis, poly(glycerol phosphate) wall teichoic acid biosynthesis, poly(ribitol phosphate) wall teichoic acid biosynthesis I (B. subtilis), poly(ribitol phosphate) wall teichoic acid biosynthesis II (S. aureus), UDP-N-acetyl-alpha-D-mannosaminouronate biosynthesis
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SYSTEMATIC NAME
IUBMB Comments
UDP-N-acetyl-alpha-D-glucosamine 2-epimerase
This bacterial enzyme catalyses the reversible interconversion of UDP-GlcNAc and UDP-ManNAc. The latter is used in a variety of bacterial polysaccharide biosyntheses.
cf. EC 3.2.1.183, UDP-N-acetylglucosamine 2-epimerase (hydrolysing).
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CAS REGISTRY NUMBER
COMMENTARY
9037-71-2
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
dihydropyrimidine-2,4(1H,3H)-dione-alpha-D-ribofuranosyl-5'-diphospho-2-acetamido-2-deoxy-alpha-D-mannopyranoside
?
uridine 5'-diphospho-2-propionamido-2-deoxy-alpha-D-mannopyranoside
?
Neisseria meningitidis serogroup A / serotype 4A
-
-
-
?
uridine 5'-diphospho-N-trifluoroaceto-2-deoxy-alpha-D-mannopyranoside
?
Neisseria meningitidis serogroup A / serotype 4A
-
-
-
?
dihydropyrimidine-2,4(1H,3H)-dione-alpha-D-ribofuranosyl-5'-diphospho-2-acetamido-2-deoxy-alpha-D-mannopyranoside
?
Neisseria meningitidis serogroup A / serotype 4A
-
-
-
?
dihydropyrimidine-2,4(1H,3H)-dione-alpha-D-ribofuranosyl-5'-diphospho-2-acetamido-2-deoxy-alpha-D-mannopyranoside
?
Neisseria meningitidis serogroup A / serotype 4A Z2491
-
-
-
?
UDP-N-acetyl-alpha-D-glucosamine
UDP-N-acetyl-alpha-D-mannosamine
-
-
-
r
UDP-N-acetyl-alpha-D-glucosamine
UDP-N-acetyl-alpha-D-mannosamine
allosteric regulatory mechanism, which involves direct interaction between one substrate molecule in the active site and another in the allosteric site
-
-
r
UDP-N-acetyl-alpha-D-glucosamine
UDP-N-acetyl-alpha-D-mannosamine
-
-
-
r
UDP-N-acetyl-alpha-D-glucosamine
UDP-N-acetyl-alpha-D-mannosamine
UDP-GlcNAc binding structure, overview
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-
r
UDP-N-acetyl-alpha-D-glucosamine
UDP-N-acetyl-alpha-D-mannosamine
-
-
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r
UDP-N-acetyl-alpha-D-glucosamine
UDP-N-acetyl-alpha-D-mannosamine
UDP-GlcNAc binding structure, overview
-
-
r
UDP-N-acetyl-alpha-D-glucosamine
UDP-N-acetyl-alpha-D-mannosamine
-
-
-
-
r
UDP-N-acetyl-alpha-D-glucosamine
UDP-N-acetyl-alpha-D-mannosamine
-
UDP-GlcNAc binding structure, overview
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r
UDP-N-acetyl-alpha-D-glucosamine
UDP-N-acetyl-alpha-D-mannosamine
Neisseria meningitidis serogroup A / serotype 4A
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-
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r
UDP-N-acetyl-alpha-D-glucosamine
UDP-N-acetyl-alpha-D-mannosamine
Neisseria meningitidis serogroup A / serotype 4A Z2491
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-
-
r
UDP-N-acetyl-alpha-D-glucosamine
UDP-N-acetyl-alpha-D-mannosamine
Q9REV4
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-
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r
UDP-N-acetyl-alpha-D-glucosamine
UDP-N-acetyl-alpha-D-mannosamine
Q9REV4
allosteric regulatory mechanism, which involves direct interaction between one substrate molecule in the active site and another in the allosteric site
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r
UDP-N-acetyl-alpha-D-mannosamine
UDP-N-acetyl-alpha-D-glucosamine
Neisseria meningitidis serogroup A / serotype 4A
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-
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r
UDP-N-acetyl-alpha-D-mannosamine
UDP-N-acetyl-alpha-D-glucosamine
Neisseria meningitidis serogroup A / serotype 4A Z2491
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-
-
r
UDP-N-acetyl-D-glucosamine
?
-
UDP-N-acetyl-D-glucosamine 2-epimerase and UDP-N-acetyl-D-mannosamine dehydrogenase are responsible for the formation of UDP-N-acetyl-D-mannosaminuronic acid from UDP-N-acetyl-D-glucosamine
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UDP-N-acetyl-D-glucosamine
?
-
enzyme of the N-acetylneuraminic acid metabolic pathway
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UDP-N-acetyl-D-glucosamine
?
-
enzyme of biosynthesis of N-acetylneuraminic acid
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UDP-N-acetyl-D-glucosamine
?
-
initial enzyme responsible for the biosynthesis of CMP-N-acetylneuraminic acid
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UDP-N-acetyl-D-glucosamine
?
-
possible role in the biogenesis of N-acetylmannosamine-containing macromolecules
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-
UDP-N-acetyl-D-glucosamine
UDP + N-acetyl-D-mannosamine
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the reverse reaction with UDP-N-acetylmannosamine requires the presence of UDP-N-acetylglucosamine
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UDP-N-acetyl-D-glucosamine
UDP + N-acetyl-D-mannosamine
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the reverse reaction with UDP-N-acetylmannosamine requires the presence of UDP-N-acetylglucosamine
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UDP-N-acetyl-D-glucosamine
UDP + N-acetyl-D-mannosamine
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the reverse reaction with UDP-N-acetylmannosamine requires the presence of UDP-N-acetylglucosamine
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-
-
UDP-N-acetyl-D-glucosamine
UDP + N-acetyl-D-mannosamine
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the reverse reaction with UDP-N-acetylmannosamine requires the presence of UDP-N-acetylglucosamine
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UDP-N-acetyl-D-glucosamine
UDP + N-acetyl-D-mannosamine
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reduction of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase activity and sialylation in distal myopathy with rimmed vacuoles
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-
?
UDP-N-acetyl-D-glucosamine
UDP + N-acetyl-D-mannosamine
-
first step of sialic acid biosynthesis
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?
UDP-N-acetyl-D-glucosamine
UDP + N-acetyl-D-mannosamine
-
mechanism involves an anti elimination of UDP to form 2-acetamidoglucal as an intermediate, followed by syn-addition of water
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?
UDP-N-acetyl-D-glucosamine
UDP + N-acetyl-D-mannosamine
-
first step of sialic acid biosynthesis
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?
UDP-N-acetyl-D-glucosamine
UDP + N-acetyl-D-mannosamine
-
mechanism involves an anti elimination of UDP to form 2-acetamidoglucal as an intermediate, followed by syn-addition of water
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-
?
UDP-N-acetyl-D-glucosamine
UDP + N-acetyl-D-mannosamine
-
reversibility is not detected
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-
UDP-N-acetyl-D-glucosamine
UDP + N-acetyl-D-mannosamine
-
reversibility is not detected
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UDP-N-acetyl-D-glucosamine
UDP + N-acetyl-D-mannosamine
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key enzyme of sialic acid biosynthesis
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?
UDP-N-acetyl-D-glucosamine
UDP + N-acetyl-D-mannosamine
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characterization of ligand binding to the bifunctional enzyme
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?
UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-D-mannosamine
-
non-hydrolizing
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?
UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-D-mannosamine
-
-
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r
UDP-N-acetyl-D-glucosamine + H2O
UDP + N-acetylmannosamine
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-
-
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?
UDP-N-acetyl-D-glucosamine + H2O
UDP + N-acetylmannosamine
epimerase active site amino acid residues D21, G111, H132, G136 and D144 are required for stabilization of the active site structure, residues R19, S301 and E307 are involved in binding of the UDP portion of the substrate. Amino acid residues K24, P27, M29, D112, E134, D143, D144, R147, S302 and R113 are located in vicinity of the active site, while residues G182 and D187 are part of the active site hinge region. The possible general catalyst is residue H220, and residues H45 and H132 are required for 2-epimerase activity
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-
?
uridine 5'-diphospho-2-hydroxyacetamido-2-deoxy-alpha-D-mannopyranoside
?
Neisseria meningitidis serogroup A / serotype 4A
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-
-
?
uridine 5'-diphospho-2-hydroxyacetamido-2-deoxy-alpha-D-mannopyranoside
?
Neisseria meningitidis serogroup A / serotype 4A Z2491
-
-
-
?
additional information
?
-
-
3'-deoxy-UDP-N-acetylglucosamine is not a substrate
-
-
-
additional information
?
-
key enzyme for biosynthesis of N-acetylneuraminate is the bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, catalyzing the first two steps of the biosynthesis in the cytosol
-
?
additional information
?
-
-
rate-limiting step in sialic acid biosynthesis pathway. The enzyme is the major determinant of cell surface sialylation in hematopoietic cell lines and is a critical regulator of the function of specific cell surface adhesion molecules
-
?
additional information
?
-
-
downregulation of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase in hyposialylated HIV-infected T cells with consequential glycosylation modification (the deficiency can be entirely corrected by nutrient complementation with N-acetylmannosamine). The promoter of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase is de novo hypermethylated in HIV-infected CEM cells
-
-
-
additional information
?
-
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the bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase is a rate-limiting enzyme of sialic acid biosynthesis
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-
-
additional information
?
-
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the homozygous M712T mutation of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase results in reduced enzyme activities but not in altered overall cellular sialylation in hereditary inclusion body myopathy
-
-
-
additional information
?
-
-
role of splice variant GNE1 in basic supply of cells with sialic acids, whereas GNE2 and GNE3 may have a function in finetuning of the sialic acid pathway
-
-
-
additional information
?
-
-
GNE interacts with proteins involved in the regulation of development, e.g. the transcription factor promyelotic leukemia zinc finger protein, which might play a crucial role in the hereditary inclusion body myopathy. GNE is regulated by a variety of biochemical means, including tetramerization promoted by the substrate UDP-GlcNAc, phosphorylation by protein kinase C and feedback inhibition by CMP-Neu5Ac, which is defect in the human disease sialuria. Multienzyme complexes of GNE with the other enzymes of the sialic acid biosynthesis pathway, either close to the Golgi CMP sialic acid transporter or in particular with the nuclear localized CMP-sialic acid synthetase, are possible
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-
-
additional information
?
-
-
GNE is a bifunctional enzyme with UDP-GlcNAc 2-epimerase and ManNAc kinase activities
-
-
-
additional information
?
-
-
GNE is a bifunctional enzyme with UDP-GlcNAc 2-epimerase and ManNAc kinase activities
-
-
-
additional information
?
-
-
GNE is a bifunctional enzyme with UDP-GlcNAc 2-epimerase and ManNAc kinase activities
-
-
-
additional information
?
-
GNE is a bifunctional enzyme with UDP-GlcNAc 2-epimerase and ManNAc kinase activities
-
-
-
additional information
?
-
-
role of splice variant GNE1 in basic supply of cells with sialic acids, whereas GNE2 and GNE3 may have a function in finetuning of the sialic acid pathway. No significant differences in activities of splice variants mGNE 1 and mGNE2
-
-
-
additional information
?
-
-
GNE interacts with proteins involved in the regulation of development, e.g. the transcription factor promyelotic leukemia zinc finger protein, which might play a crucial role in the hereditary inclusion body myopathy. GNE is regulated by a variety of biochemical means, including tetramerization promoted by the substrate UDP-GlcNAc, phosphorylation by protein kinase C and feedback inhibition by CMP-Neu5Ac. Multienzyme complexes of GNE with the other enzymes of the sialic acid biosynthesis pathway, either close to the Golgi CMP sialic acid transporter or in particular with the nuclear localized CMP-sialic acid synthetase, are possible
-
-
-
additional information
?
-
-
GNE is a bifunctional enzyme with UDP-GlcNAc 2-epimerase and ManNAc kinase activities
-
-
-
additional information
?
-
-
GNE is a bifunctional enzyme with UDP-GlcNAc 2-epimerase and ManNAc kinase activities
-
-
-
additional information
?
-
Neisseria meningitidis serogroup A / serotype 4A
substrate specificity, overview. Recombinant His6-tagged NmSacA-His6 can tolerate several chemoenzymatically synthesized UDP-ManNAc derivatives as substrates in the absence of UDP-GlcNAc although its activity is much lower than with non-modified UDP-ManNAc. Homology modeling and molecular docking. The formation of UDP-GlcNAc or UDP-ManNAc is not observed by incubating NmSacA-His6 with 2-acetamidoglucal and UDP in contrast to the serogroup B enzyme. No enzyme activity with UDP-mannose, UDP-ManF, UDP-ManN3, UDP-ManNH2, uridine 5'-diphospho-2-butyramido-2-deoxy-alpha-D-mannopyranoside, uridine 5'-diphospho-2-azidoacetamido-2-deoxy-alpha-D-mannopyranoside, uridine 5'-diphospho-2-phenylacetamido-2-deoxy-alpha-D-mannopyranoside, dihydropyrimidine-2, 4(1H,3H)-dione-alpha-D-ribofuranosyl-5'-diphospho-2-azidoxyacetamido-2-deoxy-alpha-D-mannopyranoside, and uridine 5'-diphospho-2-azidoacetamido-2-deoxy-alpha-D-glucopyranoside, docking study
-
-
-
additional information
?
-
Neisseria meningitidis serogroup A / serotype 4A Z2491
substrate specificity, overview. Recombinant His6-tagged NmSacA-His6 can tolerate several chemoenzymatically synthesized UDP-ManNAc derivatives as substrates in the absence of UDP-GlcNAc although its activity is much lower than with non-modified UDP-ManNAc. Homology modeling and molecular docking. The formation of UDP-GlcNAc or UDP-ManNAc is not observed by incubating NmSacA-His6 with 2-acetamidoglucal and UDP in contrast to the serogroup B enzyme. No enzyme activity with UDP-mannose, UDP-ManF, UDP-ManN3, UDP-ManNH2, uridine 5'-diphospho-2-butyramido-2-deoxy-alpha-D-mannopyranoside, uridine 5'-diphospho-2-azidoacetamido-2-deoxy-alpha-D-mannopyranoside, uridine 5'-diphospho-2-phenylacetamido-2-deoxy-alpha-D-mannopyranoside, dihydropyrimidine-2, 4(1H,3H)-dione-alpha-D-ribofuranosyl-5'-diphospho-2-azidoxyacetamido-2-deoxy-alpha-D-mannopyranoside, and uridine 5'-diphospho-2-azidoacetamido-2-deoxy-alpha-D-glucopyranoside, docking study
-
-
-
additional information
?
-
-
bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
-
?
additional information
?
-
-
enzyme catalyzes the first step in synthesis of sialic acids
-
?
additional information
?
-
-
reaction mechanism involving an anti-elimination of UDP to give 2-acetamidoglucal, followed by a syn-addition of water
-
?
additional information
?
-
-
key enzyme of N-acetylneuraminic acid biosynthesis
-
?
additional information
?
-
-
the bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/ManNAc kinase catalyzes the first two steps in the biosynthesis of the sialic acids
-
?
additional information
?
-
-
the enzyme catalyzes the first step of sialic acid biosynthesis
-
?
additional information
?
-
-
GNE interacts with proteins involved in the regulation of development, e.g. the transcription factor promyelotic leukemia zinc finger protein, which might play a crucial role in the hereditary inclusion body myopathy. GNE is regulated by a variety of biochemical means, including tetramerization promoted by the substrate UDP-GlcNAc, phosphorylation by protein kinase C and feedback inhibition by CMP-Neu5Ac. Multienzyme complexes of GNE with the other enzymes of the sialic acid biosynthesis pathway, either close to the Golgi CMP sialic acid transporter or in particular with the nuclear localized CMP-sialic acid synthetase, are possible
-
-
-
additional information
?
-
-
GNE is a bifunctional enzyme with UDP-GlcNAc 2-epimerase and ManNAc kinase activities
-
-
-
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
UDP-N-acetyl-alpha-D-glucosamine
UDP-N-acetyl-alpha-D-mannosamine
Q81K32, Q81X16
-
-
-
r
UDP-N-acetyl-alpha-D-glucosamine
UDP-N-acetyl-alpha-D-mannosamine
Q81K32
allosteric regulatory mechanism, which involves direct interaction between one substrate molecule in the active site and another in the allosteric site
-
-
r
UDP-N-acetyl-alpha-D-glucosamine
UDP-N-acetyl-alpha-D-mannosamine
P39131
-
-
-
r
UDP-N-acetyl-alpha-D-glucosamine
UDP-N-acetyl-alpha-D-mannosamine
P39131
-
-
-
r
UDP-N-acetyl-alpha-D-glucosamine
UDP-N-acetyl-alpha-D-mannosamine
-
-
-
-
r
UDP-N-acetyl-alpha-D-glucosamine
UDP-N-acetyl-alpha-D-mannosamine
Neisseria meningitidis serogroup A / serotype 4A
A0A0U1RGY0
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UDP-N-acetyl-alpha-D-glucosamine
UDP-N-acetyl-alpha-D-mannosamine
Neisseria meningitidis serogroup A / serotype 4A Z2491
A0A0U1RGY0
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r
UDP-N-acetyl-alpha-D-glucosamine
UDP-N-acetyl-alpha-D-mannosamine
Q9REV4
allosteric regulatory mechanism, which involves direct interaction between one substrate molecule in the active site and another in the allosteric site
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UDP-N-acetyl-D-glucosamine
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UDP-N-acetyl-D-glucosamine 2-epimerase and UDP-N-acetyl-D-mannosamine dehydrogenase are responsible for the formation of UDP-N-acetyl-D-mannosaminuronic acid from UDP-N-acetyl-D-glucosamine
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UDP-N-acetyl-D-glucosamine
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enzyme of the N-acetylneuraminic acid metabolic pathway
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UDP-N-acetyl-D-glucosamine
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enzyme of biosynthesis of N-acetylneuraminic acid
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UDP-N-acetyl-D-glucosamine
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initial enzyme responsible for the biosynthesis of CMP-N-acetylneuraminic acid
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UDP-N-acetyl-D-glucosamine
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possible role in the biogenesis of N-acetylmannosamine-containing macromolecules
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UDP-N-acetyl-D-glucosamine
UDP + N-acetyl-D-mannosamine
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reduction of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase activity and sialylation in distal myopathy with rimmed vacuoles
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UDP-N-acetyl-D-glucosamine
UDP + N-acetyl-D-mannosamine
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first step of sialic acid biosynthesis
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UDP-N-acetyl-D-glucosamine
UDP + N-acetyl-D-mannosamine
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first step of sialic acid biosynthesis
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UDP-N-acetyl-D-glucosamine
UDP + N-acetyl-D-mannosamine
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key enzyme of sialic acid biosynthesis
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UDP-N-acetyl-D-glucosamine + H2O
UDP + N-acetylmannosamine
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additional information
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Q9Y223
key enzyme for biosynthesis of N-acetylneuraminate is the bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, catalyzing the first two steps of the biosynthesis in the cytosol
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additional information
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rate-limiting step in sialic acid biosynthesis pathway. The enzyme is the major determinant of cell surface sialylation in hematopoietic cell lines and is a critical regulator of the function of specific cell surface adhesion molecules
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additional information
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downregulation of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase in hyposialylated HIV-infected T cells with consequential glycosylation modification (the deficiency can be entirely corrected by nutrient complementation with N-acetylmannosamine). The promoter of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase is de novo hypermethylated in HIV-infected CEM cells
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additional information
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the bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase is a rate-limiting enzyme of sialic acid biosynthesis
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additional information
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the homozygous M712T mutation of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase results in reduced enzyme activities but not in altered overall cellular sialylation in hereditary inclusion body myopathy
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additional information
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role of splice variant GNE1 in basic supply of cells with sialic acids, whereas GNE2 and GNE3 may have a function in finetuning of the sialic acid pathway
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additional information
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GNE interacts with proteins involved in the regulation of development, e.g. the transcription factor promyelotic leukemia zinc finger protein, which might play a crucial role in the hereditary inclusion body myopathy. GNE is regulated by a variety of biochemical means, including tetramerization promoted by the substrate UDP-GlcNAc, phosphorylation by protein kinase C and feedback inhibition by CMP-Neu5Ac, which is defect in the human disease sialuria. Multienzyme complexes of GNE with the other enzymes of the sialic acid biosynthesis pathway, either close to the Golgi CMP sialic acid transporter or in particular with the nuclear localized CMP-sialic acid synthetase, are possible
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additional information
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role of splice variant GNE1 in basic supply of cells with sialic acids, whereas GNE2 and GNE3 may have a function in finetuning of the sialic acid pathway. No significant differences in activities of splice variants mGNE 1 and mGNE2
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additional information
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GNE interacts with proteins involved in the regulation of development, e.g. the transcription factor promyelotic leukemia zinc finger protein, which might play a crucial role in the hereditary inclusion body myopathy. GNE is regulated by a variety of biochemical means, including tetramerization promoted by the substrate UDP-GlcNAc, phosphorylation by protein kinase C and feedback inhibition by CMP-Neu5Ac. Multienzyme complexes of GNE with the other enzymes of the sialic acid biosynthesis pathway, either close to the Golgi CMP sialic acid transporter or in particular with the nuclear localized CMP-sialic acid synthetase, are possible
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additional information
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key enzyme of N-acetylneuraminic acid biosynthesis
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additional information
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the bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/ManNAc kinase catalyzes the first two steps in the biosynthesis of the sialic acids
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additional information
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the enzyme catalyzes the first step of sialic acid biosynthesis
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additional information
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GNE interacts with proteins involved in the regulation of development, e.g. the transcription factor promyelotic leukemia zinc finger protein, which might play a crucial role in the hereditary inclusion body myopathy. GNE is regulated by a variety of biochemical means, including tetramerization promoted by the substrate UDP-GlcNAc, phosphorylation by protein kinase C and feedback inhibition by CMP-Neu5Ac. Multienzyme complexes of GNE with the other enzymes of the sialic acid biosynthesis pathway, either close to the Golgi CMP sialic acid transporter or in particular with the nuclear localized CMP-sialic acid synthetase, are possible
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
Neisseria meningitidis serogroup A / serotype 4A
the 2-epimerase activity of NmSacA-His6 is not dependent on the addition of an external divalent metal ion, Li+ and EDTA have no effect on enzyme activity
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2S)-2-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanamide
(2S)-2-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
(2S)-2-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]butanoic acid
(2S)-2-[(4E)-4-[[5-(3,4-dichlorophenyl)thiophen-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
(2S)-2-[(4E)-4-[[5-(3,5-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
(2S)-2-[(4E)-4-[[5-(3-chloro-4-methoxyphenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
(2S)-2-[(4E)-4-[[5-(3-chlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
(2S)-2-[(4E)-4-[[5-(4-bromo-3-chlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
(2S)-2-[(4E)-4-[[5-(4-bromo-3-chlorophenyl)thiophen-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
(2S)-2-[(4E)-4-[[5-(4-bromophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
(2S)-2-[(4E)-4-[[5-(4-bromophenyl)thiophen-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
(2S)-2-[(4E)-4-[[5-(4-chlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
(2S)-2-[(4E)-4-[[5-(4-chlorophenyl)thiophen-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
(2S)-2-[(4E)-4-[[5-(4-fluorophenyl)thiophen-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
(2S)-2-[(4E)-4-[[5-(4-iodophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
(2S)-2-[(4E)-4-[[5-(4-methoxyphenyl)thiophen-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
(2S)-2-[(4E)-5-oxo-2-thioxo-4-([5-[4-(trifluoromethoxy)phenyl]furan-2-yl]methylidene)imidazolidin-1-yl]-3-phenylpropanoic acid
(2S)-2-[(4E)-5-oxo-4-[(5-phenylfuran-2-yl)methylidene]-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
2',3'-dialdehydro-ADP
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efficient inhibition is most likely due to the structural similarity to o-UDP and not to an allosteric effect via the ATP binding site
2',3'-dialdehydro-UDP-alpha-D-N-acetylglucosamine
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0.05 mM, 70% inhibition after 30 min. 0.25 mM, 90% inhibition. Covalently bound to amino acids in the active site causing an irreversible inhibition. Effective inhibitor may serve as a basis for the chemical synthesis of further inhibitors
CMP-sialic acid
GNE/MNK is feedback inhibited by binding of the downstream product, CMP-sialic acid, in its allosteric site. The allosteric regulation by CMP-sialic acid involves residues D255, E260, R263, R266, K268, and N275
ethyl (2S)-2-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoate
Q9REV4
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ethyl (2S)-2-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoates
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N-[1-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-2-phenylethyl]-1,1,1-trifluoromethanesulfonamide
N-[1-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-2-phenylethyl]methanesulfonamide
N-[1-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]propyl]methanesulfonamide
uridine 5'-(3-acetamido-3-deoxy-2-O-methyl-alpha-D-gluco-hept-2-ulopyranos-1-yl diphosphate)
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uridine 5'-(3-acetamido-3-deoxy-2-O-methyl-alpha-D-manno-hept-2-ulopyranos-1-yl diphosphate)
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weak
uridine 5'-[(Z)-2,6-anhydro-1-deoxy-D-galactohept-1-enitol-1-yl phosphono] phosphate
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weak
uridine 5'-[(Z)-2,6-anhydro-1-deoxy-D-glucohept-1-enitol-1-yl phosphono] phosphate
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uridine 5'-[(Z)-2,6-anhydro-1-deoxy-D-mannohept-1-enitol-1-yl phosphono] phosphate
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uridine 5'-[(Z)-3-acetamido-2,6-anhydro-1,3-dideoxy-D-arabino-hept-1-enitol-1-yl phosphono] phosphate
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uridine 5'-[(Z)-3-acetamido-2,6-anhydro-1,3-dideoxy-D-gluco-hept-1-enitol-1-yl phosphono] phosphate
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[1-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-2-phenylethyl]cyanamide
(2S)-2-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanamide
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(2S)-2-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanamide
Q9REV4
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(2S)-2-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
; i.e. Epimerox, 2-epimerase inhibition through a target-specific mechanism, in vivo efficacy against Staphylococcus aureus and Bacillus anthracis
(2S)-2-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
Q9REV4
; i.e. Epimerox, 2-epimerase inhibition through a target-specific mechanism, in vivo efficacy against Staphylococcus aureus and Bacillus anthracis
(2S)-2-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]butanoic acid
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(2S)-2-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]butanoic acid
Q9REV4
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(2S)-2-[(4E)-4-[[5-(3,4-dichlorophenyl)thiophen-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
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(2S)-2-[(4E)-4-[[5-(3,4-dichlorophenyl)thiophen-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
Q9REV4
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(2S)-2-[(4E)-4-[[5-(3,5-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
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(2S)-2-[(4E)-4-[[5-(3,5-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
Q9REV4
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(2S)-2-[(4E)-4-[[5-(3-chloro-4-methoxyphenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
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(2S)-2-[(4E)-4-[[5-(3-chloro-4-methoxyphenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
Q9REV4
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(2S)-2-[(4E)-4-[[5-(3-chlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
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(2S)-2-[(4E)-4-[[5-(3-chlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
Q9REV4
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(2S)-2-[(4E)-4-[[5-(4-bromo-3-chlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
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(2S)-2-[(4E)-4-[[5-(4-bromo-3-chlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
Q9REV4
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(2S)-2-[(4E)-4-[[5-(4-bromo-3-chlorophenyl)thiophen-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
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(2S)-2-[(4E)-4-[[5-(4-bromo-3-chlorophenyl)thiophen-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
Q9REV4
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(2S)-2-[(4E)-4-[[5-(4-bromophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
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(2S)-2-[(4E)-4-[[5-(4-bromophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
Q9REV4
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(2S)-2-[(4E)-4-[[5-(4-bromophenyl)thiophen-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
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(2S)-2-[(4E)-4-[[5-(4-bromophenyl)thiophen-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
Q9REV4
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(2S)-2-[(4E)-4-[[5-(4-chlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
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(2S)-2-[(4E)-4-[[5-(4-chlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
Q9REV4
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(2S)-2-[(4E)-4-[[5-(4-chlorophenyl)thiophen-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
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(2S)-2-[(4E)-4-[[5-(4-chlorophenyl)thiophen-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
Q9REV4
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(2S)-2-[(4E)-4-[[5-(4-fluorophenyl)thiophen-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
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(2S)-2-[(4E)-4-[[5-(4-fluorophenyl)thiophen-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
Q9REV4
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(2S)-2-[(4E)-4-[[5-(4-iodophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
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(2S)-2-[(4E)-4-[[5-(4-iodophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
Q9REV4
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(2S)-2-[(4E)-4-[[5-(4-methoxyphenyl)thiophen-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
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(2S)-2-[(4E)-4-[[5-(4-methoxyphenyl)thiophen-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
Q9REV4
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(2S)-2-[(4E)-5-oxo-2-thioxo-4-([5-[4-(trifluoromethoxy)phenyl]furan-2-yl]methylidene)imidazolidin-1-yl]-3-phenylpropanoic acid
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(2S)-2-[(4E)-5-oxo-2-thioxo-4-([5-[4-(trifluoromethoxy)phenyl]furan-2-yl]methylidene)imidazolidin-1-yl]-3-phenylpropanoic acid
Q9REV4
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(2S)-2-[(4E)-5-oxo-4-[(5-phenylfuran-2-yl)methylidene]-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
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(2S)-2-[(4E)-5-oxo-4-[(5-phenylfuran-2-yl)methylidene]-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid
Q9REV4
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Mn2+
Neisseria meningitidis serogroup A / serotype 4A
leads to enzyme precipitation at 10 mM
N-[1-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-2-phenylethyl]-1,1,1-trifluoromethanesulfonamide
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N-[1-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-2-phenylethyl]-1,1,1-trifluoromethanesulfonamide
Q9REV4
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N-[1-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-2-phenylethyl]methanesulfonamide
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N-[1-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-2-phenylethyl]methanesulfonamide
Q9REV4
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N-[1-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]propyl]methanesulfonamide
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N-[1-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]propyl]methanesulfonamide
Q9REV4
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Zn2+
Neisseria meningitidis serogroup A / serotype 4A
leads to enzyme precipitation at 10 mM
[1-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-2-phenylethyl]cyanamide
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[1-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-2-phenylethyl]cyanamide
Q9REV4
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additional information
synthesis and evaluation of specific inhibitors, overview
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additional information
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UDP-glycal derivatives as transition state analogues of GNE substrates are synthesized, especially UDP-exo-glycal derivatives, C-glycosidic derivatives of 2-acetamidoglucal, and ketosides as bisubstrate analogues and bis-product analogues, respectively. Derivatives of 1-deoxyiminosugars with and without substitution of the iminogroup in the ring are promising GNE inhibitors, designed as transition-state analogues of the known enzymatic mechanism of UDP-GlcNAc 2-epimerase
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additional information
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UDP-glycal derivatives as transition state analogues of GNE substrates are synthesized, especially UDP-exo-glycal derivatives, C-glycosidic derivatives of 2-acetamidoglucal, and ketosides as bisubstrate analogues and bis-product analogues, respectively. Derivatives of 1-deoxyiminosugars with and without substitution of the iminogroup in the ring are promising GNE inhibitors, designed as transition-state analogues of the known enzymatic mechanism of UDP-GlcNAc 2-epimerase
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additional information
Neisseria meningitidis serogroup A / serotype 4A
both 2-acetamidoglucal and UDP show competitive inhibitory effects for the UDP-ManNAc 2-epimerization of NmSacA-His6. No inhibition by EDTA, and 1 mM DTT
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additional information
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UDP-glycal derivatives as transition state analogues of GNE substrates are synthesized, especially UDP-exo-glycal derivatives, C-glycosidic derivatives of 2-acetamidoglucal, and ketosides as bissubstrate analogues and bis-product analogues, respectively. Derivatives of 1-deoxyiminosugars with and without substitution of the iminogroup in the ring are promising GNE inhibitors, designed as transition-state analogues of the known enzymatic mechanism of UDP-GlcNAc 2-epimerase
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additional information
Q9REV4
synthesis and evaluation of specific inhibitors, overview
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
UDP-GlcNAc
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allosteric activitation by substrate via direct interactions between UDP and substrate
UDP-GlcNAc
Neisseria meningitidis serogroup A / serotype 4A
allosteric activator, absolutely required for their UDP-ManNAc 2-epimerization catalytic activity, activates recombinant His6-tagged enzyme NmSacA
UDP-N-acetylglucosamine
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the reverse reaction with UDP-N-acetylmannosamine requires the presence of UDP-N-acetylglucosamine
UDP-N-acetylglucosamine
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the reverse reaction with UDP-N-acetylmannosamine requires the presence of UDP-N-acetylglucosamine
additional information
Neisseria meningitidis serogroup A / serotype 4A
no activation by EDTA, and 1 mM DTT
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Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3.6
UDP-N-acetyl-alpha-D-glucosamine
Neisseria meningitidis serogroup A / serotype 4A
pH 8.5, 37°C, recombinant enzyme
5.2
UDP-N-acetyl-alpha-D-mannosamine
Neisseria meningitidis serogroup A / serotype 4A
pH 8.5, 37°C, recombinant enzyme
additional information
additional information
Hill coefficient of 2.7, positive cooperativity
-
0.08
UDP-N-acetyl-D-glucosamine
-
UDP-N-acetyl-D-glucosamine, liver enzyme of tumor-bearing animals
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
31
UDP-N-acetyl-alpha-D-glucosamine
Neisseria meningitidis serogroup A / serotype 4A
pH 8.5, 37°C, recombinant enzyme
52
UDP-N-acetyl-alpha-D-mannosamine
Neisseria meningitidis serogroup A / serotype 4A
pH 8.5, 37°C, recombinant enzyme
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
10
UDP-N-acetyl-alpha-D-glucosamine
Neisseria meningitidis serogroup A / serotype 4A
pH 8.5, 37°C, recombinant enzyme
8.6
UDP-N-acetyl-alpha-D-mannosamine
Neisseria meningitidis serogroup A / serotype 4A
pH 8.5, 37°C, recombinant enzyme
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
14
2-acetamidoglucal
Neisseria meningitidis serogroup A / serotype 4A
pH 8.5, 37°C, recombinant enzyme
0.8
UDP
Neisseria meningitidis serogroup A / serotype 4A
pH 8.5, 37°C, recombinant enzyme
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 11
Neisseria meningitidis serogroup A / serotype 4A
activity range with high activity
6.5 - 8.6
-
6.5: about 30% of maximal activity, 8.6: about 65% of maximal activity
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
-
-
brenda
bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, splice variant hGNE2
-
-
brenda
mutations in patients with hereditary inclusion body myopathy: G135V/R246W (GNE/GNE domain mutation), UDP-N-acetylglucosamine 2-epimerase activity is 38% of wild-type, N-acetylmannosamine kinase activity is 72% of wild-type. V216A/A631V (GNE/MNK domain mutation), UDP-N-acetylglucosamine 2-epimerase activity is 48% of wild-type, N-acetylmannosamine kinase activity is 63% of wild-type. M712T/M712T (MNK/MNK domain mutation), UDP-N-acetylglucosamine 2-epimerase activity is 83% of wild-type, N-acetylmannosamine kinase activity is 55% of wild-type
-
-
brenda
three different isozymes, hGNE1, hGNE2, and hGNE3, from the two splice variants including exon A1, The N-terminus of hGNE2 is prolonged by 31 additional amino acids. The lack of exon 2 in the cDNA encoding for hGNE3 leads to loss of the first 55 amino acids of hGNE1
-
-
brenda
bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, splice variant hGNE2
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
HIV-infected. Downregulation of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase in hyposialylated HIV-infected T cells
brenda
-
cell proliferation is directly correlated with GNE-expression and the cellular sialic acid concentration. Growth-related genes are differentially expressed in GNE-deficient embryonic stem cells compared to wild-type embryonic stem cells
brenda
-
enzyme activity is 18% of the activity found in normal livers
brenda
additional information
-
GNE2 and GNE3 display tissue-specific expression patterns
brenda
-
enzyme activity is significantly elevated at 8 h after intradermal injection of carageenan or urate crystals, falling to normal levels by day 3
brenda
-
enzyme activity is significantly elevated at 8 h after intradermal injection of carageenan or urate crystals, falling to normal levels by day 3
-
brenda
-
colonic mucosa: normal mucosa, non-malignant mucosa in azomethane treated animals, low activity in azomethane-induced tumor tissue
brenda
-
enzyme is detected only in sialoglycoprotein-secreting tissues
brenda
-
activity in colonic tissue is 25-50times lower than in liver
brenda
-
activity in colonic tissue is 25-50times lower than in liver; colonic mucosa: normal mucosa, non-malignant mucosa in azomethane treated animals, low activity in azomethane-induced tumor tissue
-
brenda
-
enzyme is detected only in sialoglycoprotein-secreting tissues
-
brenda
-
enzyme activity is low at birth, increases to a maximum value on day 15, and falls gradually until day 30, thereafter it increases up to the 60th day
brenda
-
enzyme activity is significantly elevated at 8 h after intradermal injection of carrageenan or urate crystals, falling to normal levels by day 3
brenda
-
enzyme is detected only in sialoglycoprotein-secreting tissues
brenda
-
enzyme activity is low at birth, increases to a maximum value on day 15, and falls gradually until day 30, thereafter it increases up to the 60th day
brenda
-
enzyme activity is significantly elevated at 8 h after intradermal injection of carrageenan or urate crystals, falling to normal levels by day 3
-
brenda
-
; enzyme is detected only in sialoglycoprotein-secreting tissues
-
brenda
-
enzyme is detected only in sialoglycoprotein-secreting tissues
brenda
-
enzyme is detected only in sialoglycoprotein-secreting tissues
-
brenda
-
developmentally regulated: high levels in immature myoblast but low levels in mature skeletal muscle
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
evolution
the bacterial UDP-GlcNAc-binding site is conserved and probably unique to the nonhydrolyzing bacterial 2-epimerases. Conservation of the allosteric site residues in the nonhydrolyzing bacterial 2-epimerases indicates that the allosteric regulatory mechanism, which involves direct interaction between one substrate molecule in the active site and another in the allosteric site, is used exclusively by this class of bacterial enzymes
evolution
Q9REV4
the bacterial UDP-GlcNAc-binding site is conserved and probably unique to the nonhydrolyzing bacterial 2-epimerases. Conservation of the allosteric site residues in the nonhydrolyzing bacterial 2-epimerases indicates that the allosteric regulatory mechanism, which involves direct interaction between one substrate molecule in the active site and another in the allosteric site, is used exclusively by this class of bacterial enzymes
evolution
Q81K32, Q81X16
Bacillus anthracis gneY and gneZ encode nearly identical UDP-GlcNAc 2-epimerase enzymes that catalyze the reversible conversion of UDPGlcNAc and UDP-ManNAc; Bacillus anthracis gneY and gneZ encode nearly identical UDP-GlcNAc 2-epimerase enzymes that catalyze the reversible conversion of UDPGlcNAc and UDP-ManNAc
malfunction
-
enzyme deficiency causes the disease sialuria in humans. Hereditary inclusion body myopathy, h-IBM, is also a disease caused by different mutations in the GNE gene, it is an autosomal recessive neuromuscular disorder characterized by adult onset, slowly progressive skeletal muscle weakness, and typical histological features as rimmed vacuoles and filamentous inclusions. Sialuria is caused by the loss of feedback control of UDP-GlcNAc 2-epimerase activity due to the mutation of only one of the two arginine residues 263 and 266. Sialuria leads to massive production of free Neu5Ac, which accumulates in the cytoplasm and results in mental retardation and hepatomegaly
malfunction
-
GNE deficiency can lead to hereditary inclusion body myopathy, HIBM, phenotypes, overview
malfunction
-
mutations in the GNE gene are associated with autosomal recessive hereditary inclusion body myopathy, i.e. HIBM or IBM2, a progressive adult onset muscle wasting disorder characterized by sparing of the quadriceps. IBM2 is also known as distal myopathy with rimmed vacuoles or nonaka myopathy
malfunction
GNE mutations can result in two human disorders, hereditary inclusion body myopathy, HIBM, and sialuria
malfunction
-
stable knock-down of GNE dramatically increases incorporation of N-acetylmannosamine analogues into glycoproteins of HEK-293 cells
malfunction
mutation of this enzyme causes changes in cell morphology and the thermoresistance of the cell wall
malfunction
-
mutation of this enzyme causes changes in cell morphology and the thermoresistance of the cell wall
malfunction
-
mutation of this enzyme causes changes in cell morphology and the thermoresistance of the cell wall
-
metabolism
-
the enzyme catalyzes the first two steps in the sialic acid biosynthesis, required for sialylation of diverse glycoproteins and glycolipids e.g. in skeletal muscle
metabolism
-
GNE is the rate-limiting enzyme of N-acetylneuraminate, i.e. sialic acid, biosynthesis
metabolism
-
GNE catalyzes the first two steps of sialic acid biosynthesis in the cytosol
metabolism
GNE catalyzes the first two committed, rate-limiting steps in the biosynthesis of N-acetylneuraminic acid, i.e. sialic acid
metabolism
-
the enzyme catalyzes the interconversion of UDP-N-acetyl-alpha-D-glucosamine to UDP-N-acetyl-alpha-D-mannosamine, which is used in the biosynthesis of cell surface polysaccharides in bacteria
metabolism
-
the enzyme catalyzes the interconversion of UDP-N-acetyl-alpha-D-glucosamine to UDP-N-acetyl-alpha-D-mannosamine, which is used in the biosynthesis of cell surface polysaccharides in bacteria
-
physiological function
-
the bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, GNE, is the key enzyme for the biosynthesis of N-acetylneuraminic acid, from which all other sialic acids are formed
physiological function
-
the bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, GNE, is the key enzyme for the biosynthesis of N-acetylneuraminic acid, from which all other sialic acids are formed
physiological function
-
the bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, GNE, is the key enzyme for the biosynthesis of N-acetylneuraminic acid, from which all other sialic acids are formed
physiological function
-
GNE is required for sialic acid biosynthesis, the sialic acid pathway and the respective sialic acid precursors such as ManNAc do regulate the MAP kinase signalling pathway, influencing processes like cell proliferation, overview
physiological function
Neisseria meningitidis serogroup A / serotype 4A
SacA is proposed to be involved in the first step in serogroup A capsular polysaccharides (CPS) biosynthetic pathway and is critical for serogroup A CPS biosynthesis. It catalyzes the interconversion between UDP-GlcNAc and UDP-ManNAc. This epimerization process is independent of nicotinamide adenine dinucleotide oxidized form (NAD+) and is critical for synthesizing bacterial ManNAc-containing CPSs
physiological function
Q81K32, Q81X16
GneZ, a UDP-GlcNAc 2-epimerase, is required for S-layer assembly and vegetative growth of Bacillus anthracis. Gene gneZ, but not gneY, is required for Bacillus anthracis vegetative growth, rod cell shape, S-layer assembly, and synthesis of pyruvylated secondary cell wall polysaccharide (SCWP). Nevertheless, inducible expression of gneY alleviates all the defects associated with the gneZ mutant. In contrast to vegetative growth, neither germination of Bacillus anthracis spores nor the formation of spores in mother cells require UDP-GlcNAc 2-epimerase activity. UDP-GlcNAc 2-epimerase enzymes have been shown to be required for the attachment of the phage lysin PlyG with the bacterial envelope and for bacterial growth. UDG-GlcNAc 2-epimerase activity, i.e., the expression of either gneY or gneZ, is not required for B. anthracis spore formation; GneZ, a UDP-GlcNAc 2-epimerase, is required for S-layer assembly and vegetative growth of Bacillus anthracis. Gene gneZ, but not gneY, is required for Bacillus anthracis vegetative growth, rod cell shape, S-layer assembly, and synthesis of pyruvylated secondary cell wall polysaccharide (SCWP). Nevertheless, inducible expression of gneY alleviates all the defects associated with the gneZ mutant. In contrast to vegetative growth, neither germination of Bacillus anthracis spores nor the formation of spores in mother cells require UDP-GlcNAc 2-epimerase activity. UDP-GlcNAc 2-epimerase enzymes have been shown to be required for the attachment of the phage lysin PlyG with the bacterial envelope and for bacterial growth. UDG-GlcNAc 2-epimerase activity, i.e., the expression of either gneY or gneZ, is not required for B. anthracis spore formation
physiological function
UDP-GlcNAc 2-epimerase catalyzes the interconversion of UDP-GlcNAc to UDP-ManNAc, which is used in the biosynthesis of cell surface polysaccharides in bacteria
physiological function
-
UDP-GlcNAc 2-epimerase catalyzes the interconversion of UDP-GlcNAc to UDP-ManNAc, which is used in the biosynthesis of cell surface polysaccharides in bacteria
physiological function
-
UDP-GlcNAc 2-epimerase catalyzes the interconversion of UDP-GlcNAc to UDP-ManNAc, which is used in the biosynthesis of cell surface polysaccharides in bacteria
-
physiological function
Neisseria meningitidis serogroup A / serotype 4A Z2491
-
SacA is proposed to be involved in the first step in serogroup A capsular polysaccharides (CPS) biosynthetic pathway and is critical for serogroup A CPS biosynthesis. It catalyzes the interconversion between UDP-GlcNAc and UDP-ManNAc. This epimerization process is independent of nicotinamide adenine dinucleotide oxidized form (NAD+) and is critical for synthesizing bacterial ManNAc-containing CPSs
-
additional information
Neisseria meningitidis serogroup A / serotype 4A
of the six major disease-causing Neisseria meningitidis serogroups, only serogroups A and X produce capsular polysaccharides (CPSs) that do not have N-acetylneuraminic acid (Neu5Ac, sialic acid is a more general term) residues. Unlike the CPSs of serogroups B and C which are homopolymers of Neu5Ac with alpha2-8- and alpha2-9-linkages respectively, or serogroups W-135 and Y CPSs which are heteropolymers of [-6Gal/Glcalpha1-4Neu5Acalpha2-]n with alternating Neu5Ac and Gal/Glc as disaccharide repeating units, the CPS of serogroup A is a homopolymer of [-6ManNAcalpha1-phosphate-]n. Correspondingly, the genetic organization for serogroup A capsule is different from those for serogroups B, C, W-135, and Y
additional information
comparison of the crystal structures of Methanocaldococcus jannaschii in open and closed conformations and of Bacillus subtilis. Homologous enzyme structure comparisons, overview
additional information
-
a comparison of the crystal structures in open and closed conformations shows that upon UDP and UDPGlcNAc binding, the enzyme undergoes conformational changes involving a rigid-body movement of the C-terminal domain. Comparison of the crystal structures of Methanocaldococcus jannaschii and of Bacillus subtilis. Structural superimposition of closed-form and open-form Mj-epimerase. Homologous enzyme structure comparisons, overview
additional information
-
comparison of the crystal structures of Methanocaldococcus jannaschii in open and closed conformations and of Bacillus subtilis. Homologous enzyme structure comparisons, overview
-
additional information
Neisseria meningitidis serogroup A / serotype 4A Z2491
-
of the six major disease-causing Neisseria meningitidis serogroups, only serogroups A and X produce capsular polysaccharides (CPSs) that do not have N-acetylneuraminic acid (Neu5Ac, sialic acid is a more general term) residues. Unlike the CPSs of serogroups B and C which are homopolymers of Neu5Ac with alpha2-8- and alpha2-9-linkages respectively, or serogroups W-135 and Y CPSs which are heteropolymers of [-6Gal/Glcalpha1-4Neu5Acalpha2-]n with alternating Neu5Ac and Gal/Glc as disaccharide repeating units, the CPS of serogroup A is a homopolymer of [-6ManNAcalpha1-phosphate-]n. Correspondingly, the genetic organization for serogroup A capsule is different from those for serogroups B, C, W-135, and Y
-
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PDB
SCOP
CATH
UNIPROT
ORGANISM
Bacillus subtilis (strain 168)
Burkholderia vietnamiensis (strain G4 / LMG 22486)
Escherichia coli (strain K12)
Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e)
Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440)
Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440)
Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440)
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
40000
42400
2 * 40000, SDS-PAGE, 2 * 42400, calculated, recombinant enzyme
40000
2 * 40000, SDS-PAGE, 2 * 42400, calculated, recombinant enzyme
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
hexamer
tetramer
additional information
?
-
x * 39368, calculation from nucleotide sequence; x * 40000, SDS-PAGE
?
Neisseria meningitidis serogroup A / serotype 4A
x * 43000, recombinant His6-tagged NmSacA, SDS-PAGE
?
Neisseria meningitidis serogroup A / serotype 4A Z2491
-
x * 43000, recombinant His6-tagged NmSacA, SDS-PAGE
-
dimer
-
recombinant splice variant hGNE1, mixture of tetramers and dimers in ratio of 3:1. Recombinant splice variant hGNE2, dimer. Gel filtration expreriments
dimer
2 * 40000, SDS-PAGE, 2 * 42400, calculated, recombinant enzyme
dimer
-
recombinant splice variant mGNE1, mixture of tetramers and dimers in ratio of 4:1. Gel filtration expreriments
tetramer
-
recombinant splice variant hGNE1, mixture of tetramers and dimers in ratio of 3:1, gel filtration
tetramer
-
recombinant splice variant mGNE1, mixture of tetramers and dimers in ratio of 4:1. Splice variant mGNE2, fully tetrameric state, gel filtration expreriments
additional information
-
UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase interacts with the non-muscle form of alpha-actinin, alpha-actinin-1, in mature skeletal muscle cells
additional information
-
comparison of the GNE primary structures reveals a high sequence similarity between human and rodent GNE, indicating high evolutionary conservation
additional information
modeling of the active sites of human GNE/MNK using vailable structural data of GNE/MNK homologues, overview
additional information
-
structural superimposition of closed-form and open-form Mj-epimerase, overview
additional information
-
comparison of the GNE primary structures reveals a high sequence similarity between human and rodent GNE, indicating high evolutionary conservation
additional information
-
comparison of the GNE primary structures reveals a high sequence similarity between human and rodent GNE, indicating high evolutionary conservation
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
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CRYSTALLIZATION/commentary
ORGANISM
UNIPROT
LITERATURE
ternary complex between the UDP-GlcNAc 2-epimerase, its substrate UDP-GlcNAc and the reaction intermediate UDP, at 1.7 A resolution. Direct interactions between the substrate and UDP via two hydrogen bonds to the alpha- and beta-phosphates of the adjacent UDP molecule, and between the complex and highly conserved enzyme residues. The binding of UDP-GlcNAc is associated with conformational changes in the active site of the enzyme
-
UDP-GlcNAc 2-epimerase in complex with UDPGlcNAc and UDP, X-ray diffraction structure determination and analysis at 1.69 A resolution, molecular replacement using enzyme structure, PDB ID 3BEO, as search model
hanging drop vapor diffusion method, selenomethionyl enzyme, X-ray structure at 2.5 A of the enzyme with bound UDP
-
sitting-drop vapor-diffusion method, crystal structures in open and closed conformations. A comparison of these crystal structures shows that upon UDP and UDPGlcNAc binding, the enzyme undergoes conformational changes involving a rigid-body movement of the C-terminal domain
-
UDP-GlcNAc 2-epimerase in open and closed conformations, and UDP-GlcNAc 2-epimerase in complex with UDPGlcNAc and UDP, sitting drop vapor diffusion method, mixing of 0.001 ml of 5 mg/ml protein in 50 mM Tris-HCl, pH 8.0, 100 mM NaCl, 5% glycerol, and 2 mM tris(2-carboxyethyl)phosphine, with 0.001 ml of reservoir solution containing 40 mM Tris-propane, 60 mM citrate, pH 4.1, and 16% PEG3350, and equilibration against 0.3 ml of reservoir solution at 20°C for 1 week, X-ray diffraction structure determination and analysis at 1.42-2.85 A resolution
-
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D95N
-
about 18000 fold decrease in turnover number for UDP-N-acetyl-D-glucosamine, not possible to obtain accurate kinetic constants
E117Q
-
about 18000 fold decrease in turnover number for UDP-N-acetyl-D-glucosamine, not possible to obtain accurate kinetic constants
E131Q
-
about 18000 fold decrease in turnover number for UDP-N-acetyl-D-glucosamine, not possible to obtain accurate kinetic constants
H213N
-
30fold increase in Km-value and 50fold decrease in turnover-number for UDP-N-acetyl-D-glucosamine. Unlike the wild-type enzyme no inhibition is detected at UDP-concentrations up to 10 mM
K15A
-
more than 100fold increase in KM-value for UDP-N-acetyl-D-glucosamine
A630T
-
mutation in patients with distal myopathy with rimmed vacuoles, UDP-N-acetylglucosamine 2-epimerase activity of mutant enzyme is reduced to 70-80% of wild-type activity
A631V
-
a naturally occuring missense mutation in exon 11 of the GNE gene of a patient with hereditary inclusion body myopathy
C13S
C303V
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
C303X
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
D176V
D177C
-
mutation in patients with distal myopathy with rimmed vacuoles, UDP-N-acetylglucosamine 2-epimerase activity of mutant enzyme is reduced to less than 20% of wild-type
D225N
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
D378Y
E2G
-
a naturally occuring missense mutation in exon 2 of the GNE gene of a patient with hereditary inclusion body myopathy
G135V
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
G135V/R246W
-
mutation in patients with hereditary inclusion body myopathy: G135V/R246W (GNE/GNE domain mutation), UDP-N-acetylglucosamine 2-epimerase activity is 38% of wild-type, N-acetylmannosamine kinase activity is 72% of wild-type
G206S
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
G708S
-
mutation in patients with distal myopathy with rimmed vacuoles, UDP-N-acetylglucosamine 2-epimerase activity of mutant enzyme is reduced to 50% of wild-type activity
G89R
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
H132Q
I142T
-
a naturally occuring missense mutation in exon 3 of the GNE gene of a patient with hereditary inclusion body myopathy
I200F
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
I241S
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
I298T
-
a naturally occuring missense mutation in exon 5 of the GNE gene of a patient with hereditary inclusion body myopathy
I472T
-
mutation in patients with distal myopathy with rimmed vacuoles, UDP-N-acetylglucosamine 2-epimerase activity of mutant enzyme is reduced to 50% of wild-type activity
L379H
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
L556S
-
a naturally occuring missense mutation in exon 10 of the GNE gene of a patient with hereditary inclusion body myopathy
M171V
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
M29T
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
M712T
M712T/M712T
-
M712T/M712T (MNK/MNK domain mutation), UDP-N-acetylglucosamine 2-epimerase activity is 83% of wild-type, N-acetylmannosamine kinase activity is 55% of wild-type
P27S
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
P283S
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
P36L
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
Q436X
-
a naturally occuring nonsense mutation in exon 8 of the GNE gene of a patient with hereditary inclusion body myopathy
R11W
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
R129Q
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
R162C
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
R177C
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
R202L
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
R246Q
R246W
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
R263L
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
R266Q
R266W
R277C
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
R306Q
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
R335W
R71W
-
a naturally occuring missense mutation in exon 3 of the GNE gene of a patient with hereditary inclusion body myopathy
R8X
-
a naturally occuring nonsense mutation in exon 2 of the GNE gene of a patient with hereditary inclusion body myopathy
S615X
-
a naturally occuring nonsense mutation in exon 11 of the GNE gene of a patient with hereditary inclusion body myopathy
V216A
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
V216A/A631V
-
V216A/A631V (GNE/MNK domain mutation), UDP-N-acetylglucosamine 2-epimerase activity is 48% of wild-type, N-acetylmannosamine kinase activity is 63% of wild-type
V331A
V367I
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
V572L
-
mutation in patients with distal myopathy with rimmed vacuoles, UDP-N-acetylglucosamine 2-epimerase activity of mutant enzyme is reduced to 70-80% of wild-type activity
V696M
W204X
-
a naturally occuring nonsense mutation in exon 3 of the GNE gene of a patient with hereditary inclusion body myopathy
Y675H
-
a naturally occuring missense mutation in exon 12 of the GNE gene of a patient with hereditary inclusion body myopathy
D100N
-
no conversion of UDP-N-acetyl-D-glucosamine to UDP + N-acetyl-D-mannosamine
D131N
-
no conversion of UDP-N-acetyl-D-glucosamine to UDP + N-acetyl-D-mannosamine, acetamidoglucal is released from the active site during catalysis
E122Q
-
no conversion of UDP-N-acetyl-D-glucosamine to UDP + N-acetyl-D-mannosamine, acetamidoglucal is released from the active site during catalysis
D100N
-
no conversion of UDP-N-acetyl-D-glucosamine to UDP + N-acetyl-D-mannosamine
-
D131N
-
no conversion of UDP-N-acetyl-D-glucosamine to UDP + N-acetyl-D-mannosamine, acetamidoglucal is released from the active site during catalysis
-
E122Q
-
no conversion of UDP-N-acetyl-D-glucosamine to UDP + N-acetyl-D-mannosamine, acetamidoglucal is released from the active site during catalysis
-
D413K
-
enzyme with mutation in the putative kinase active site shows drastic loss in their kinase activity but retains their epimerase activity
D413N
-
enzyme with mutation in the putative kinase active site shows drastic loss in their kinase activity but retains their epimerase activity
H110A
-
mutant enzyme shows a drastic loss of epimerase activity, oligomerization is significantly different from that of the wild-type enzyme,loss of epimerase activity can largely by attributed to incorrect protein folding
H132A
-
mutant enzyme shows a drastic loss of epimerase activity, oligomerization is significantly different from that of the wild-type enzyme, loss of epimerase activity can largely by attributed to incorrect protein folding
H155A
-
mutant enzyme forms mainly trimeric enzyme with small amounts of hexamer; mutant enzyme shows a drastic loss of epimerase activity, loss of epimerase activity can largely by attributed to incorrect protein folding
H157A
-
mutant enzyme forms mainly trimeric enzyme with small amounts of hexamer; mutant enzyme shows a drastic loss of epimerase activity, loss of epimerase activity can largely by attributed to incorrect protein folding
R420M
-
enzyme with mutation in the putative kinase active site shows drastic loss in their kinase activity but retains their epimerase activity
additional information
C13S
-
mutation in patients with distal myopathy with rimmed vacuoles, UDP-N-acetylglucosamine 2-epimerase activity of mutant enzyme is reduced to less than 20% of wild-type
C13S
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
D176V
-
mutation in patients with distal myopathy with rimmed vacuoles, UDP-N-acetylglucosamine 2-epimerase activity of mutant enzyme is reduced to less than 20% of wild-type
D176V
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
D378Y
-
mutation in patients with distal myopathy with rimmed vacuoles, UDP-N-acetylglucosamine 2-epimerase activity of mutant enzyme is reduced to less than 20% of wild-type
D378Y
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
H132Q
-
mutation in patients with distal myopathy with rimmed vacuoles, UDP-N-acetylglucosamine 2-epimerase activity of mutant enzyme is reduced to less than 20% of wild-type
H132Q
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
M712T
-
the homozygous M712T mutation of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase results in reduced enzyme activities but not in altered overall cellular sialylation in hereditary inclusion body myopathy
M712T
the Persian-Jewish HIBM founder mutation is located at the interface alpha4alpha10 of GNE and likely affects GlcNAc, Mg2+, and ATP binding
R246Q
-
a naturally occuring missense mutation in exon 4 of the GNE gene of a patient with hereditary inclusion body myopathy
R246Q
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
R266Q
-
GNE mutants are created by site-directed mutagenesis with the mutagenic oligonucleotides 5'-GGTTCGAGTGATGCAGAAGAAGGGCATTGAGCA-3' for the R266Q sialuria mutations (where the site of mutation is underlined) through PCR-like amplification with Pfu polymerase.
R266Q
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
R266W
-
GNE mutants are created by site-directed mutagenesis with the mutagenic oligonucleotides 5'-GGTTCGAGTGATGTGGAAGAAGGGCATTGAGCA-3' for the R266W sialuria mutations (where the site of mutation is underlined) through PCR-like amplification with Pfu polymerase.
R266W
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
R335W
-
a naturally occuring missense mutation in exon 6 of the GNE gene of a patient with hereditary inclusion body myopathy
R335W
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
V331A
-
mutation in patients with distal myopathy with rimmed vacuoles, UDP-N-acetylglucosamine 2-epimerase activity of mutant enzyme is reduced to less than 20% of wild-type
V331A
a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme
V696M
-
naturally occuring missense mutation G2086A involved in hereditary inclusion body myopathy, phenotype, overview
V696M
-
a naturally occuring missense mutation in exon 12 of the GNE gene of a patient with hereditary inclusion body myopathy
additional information
-
splice variant hGNE2, recombinantly expressed in insect and mamalian cells, displays selective reduction of UDPGlcNAc 2-epimerase activity by the loss of its tetrameric state, which is essential for full enzyme activity. Splice variant hGNE3 only possesses kinase activity
additional information
-
sialuria is caused by the loss of feedback control of UDP-GlcNAc 2-epimerase activity due to the mutation of only one of the two arginine residues 263 and 266
additional information
-
the frame shif mutation 1295delA, leading to a premature stop codon at K432, is involved in hereditary inclusion body myopathy, phenotype, overview
additional information
-
a synonymous variation, p.Y591Y, codon tac>tat, is seen in a patient bearing compound heterozygous nonsynonymous mutation, p.S615X and p.Y675H
additional information
mutant genotyping, overview. Modeling of effects of GNE/MNK missense mutations associated with HIBM or sialuria on helix arrangement, substrate binding, and enzyme action, overview. All reported mutations are associated with the active sites or secondary structure interfaces of GNE/MNK
additional information
-
transgenic Arabidopsis thaliana plants expressing three key enzymes of the mammalian Neu5Ac biosynthesis pathway: UDPN-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, N-acetylneuraminic acid phosphate synthase, and CMP-Nacetylneuraminic acid synthetase. Simultaneous expression of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase and N-acetylneuraminic acid phosphate synthase results in the generation of significant Neu5Ac amounts of 1275 nmol per g fresh weight in leaves, which can be further converted to cytidine monophospho-N-acetylneuraminic acid by coexpression of CMP-N-acetylneuraminic acid synthetase
additional information
-
generation of GNE knockout mice by gene targeting, enzyme knockout leads to embryonic lethality, phenotype, overview. Impaired sialylation of glycoconjugates induces cell death, either by the loss of the sialic acid specific masking of cells to prevent proteolytic attack or by the prevention of cell migration and differentiation
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
the purified enzyme is 80% pure, no further purification because it is unstable to freezing and has limited stability upon storage at 4°C
-
UDP and UDP-N-acetylglucosamine protect the enzyme from inactivation by aging
-
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-10°C, overnight, in a saturated (NH4)2SO4 solution, approximately 20% loss of activity
-
-18°C, stable for several months
4°C, purified enzyme is 80% pure, no further purification because it is unstable to freezing and has limited stability upon storage at 4°C
-
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PURIFICATION/commentary
ORGANISM
UNIPROT
LITERATURE
enzyme expressed in Escherichia coli and enzyme expressed in insect cells
-
recombinant C-terminally His6-tagged NmSacA from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
Neisseria meningitidis serogroup A / serotype 4A
recombinant enzyme expressed in Spodoptera frugiperda cells using a baculovirus expression system
-
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity and anion exchange chromatography, gel filtration, and ultrafiltration
-
recombinant His6-tagged enzyme from Escherichia coli strain BL21(DE3)
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CLONED/commentary
ORGANISM
UNIPROT
LITERATURE
cloning of the neuC gene into an intein expression vector to facilitate purification
-
DNA sequencing of the GNE coding region of 64 symptomatic patients with autosomal recessive hereditary inclusion body myopathy, genotyping-phenotyping of patients from different ethnics, overview
-
expression in Escherichia coli
expression in Insect Cells and supercompetent InvalphaF' Escherichia coli cells (Invitrogen)
-
expression in Sf9 insect cells, wild-type enzyme and mutant enzymes DELTA1-39, DELTA1-234, DELTA1-356, DELTA383-722, DELTA490-722, DELTA597-722, DELTA697-722, DELTA717-722
-
expression of wild-type and mutant enzymes (C13S, H132Q, D176V, D177C, V331A, I472T, G708S, A631V, V572L and A630T) in COS-7 cells
-
functional expression in Escherichia coli, Saccharomyces cerevisiae, Pichia pastoris or insect cells. In all cell types, the expressed enzyme displayes both epimerase and kinase activities. In Escherichia coli up to 2 mg protein/l cell culture is expressed in yeast cells only 0.4 mg/ml, in insect cells up to 100 mg/L. In all three cell systems, insoluble protein aggregates are also observed. Expression and purification of the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase in Sf-900 cells can yield the miligram amount of protein required for structural characterization of the enzyme. The easier expression in Escherichia coli and yeast provides sufficient quantities for enzymatic and kinetic characterization
-
gene gneY, DNA and amino acid sequence determination and analysis, genetic structure, sequence comparisons; gene gneYZ, DNA and amino acid sequence determination and analysis, genetic structure, sequence comparisons
Q81K32, Q81X16
gene sacA, encoded in the serogroup A cps operon, sequence comparisons, recombinant overexpression of C-terminally His6-tagged recombinant NmSacA in Escherichia coli strain BL21(DE3)
Neisseria meningitidis serogroup A / serotype 4A
gene wecB, sequence comparisons, recombinant expression of C-terminally His6-tagged enzyme in Escherichia coli strain BL21(DE3)
gene wecB, sequence comparisons, recombinant expression of His-tagged enzyme in Escherichia coli strain BL21(DE3)
-
high level overexpression of the active enzyme is established by using the baculovirus/Sf9 system
-
overexpression in Escherichia coli BL21(DE3), wild-type enzyme and mutant enzymes D100N, E122Q and D131N
-
proteome expression analysis in wild-type and GNE-deficient embryonic stem cells, overview. GNE overexpression in HEK cells
-
splice variant hGNE2, expression in insect and mammalian cells. Splice variant hGNE3, expression in Escherichia coli
-
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
biotechnology
-
production of erythropoietin (EPO) in Chinese Hamster Ovary (CHO) cells
drug development
medicine
-
UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase interacts with the non-muscle form of alpha-actinin, alpha-actinin-1, in mature skeletal muscle cells. No significant difference in the binding of alpha-actinin-1 with either wild-type or mutant enzyme, and therefore no conclusions wether and how the interaction is relevant to the muscle-restricted pathology of hereditary inclusion body myopathy
synthesis
-
transgenic Arabidopsis thaliana plants expressing three key enzymes of the mammalian Neu5Ac biosynthesis pathway: UDPN-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, N-acetylneuraminic acid phosphate synthase, and CMP-Nacetylneuraminic acid synthetase. Simultaneous expression of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase and N-acetylneuraminic acid phosphate synthase results in the generation of significant Neu5Ac amounts of 1275 nmol per g fresh weight in leaves, which can be further converted to cytidine monophospho-N-acetylneuraminic acid by coexpression of CMP-N-acetylneuraminic acid synthetase
drug development
the enzyme is a target for development of antibiotic agent for treatment of infections caused by Gram-positive bacteria, such as Staphylococcus aureus and Bacillus anthracis
drug development
Q9REV4
the enzyme is a target for development of antibiotic agent for treatment of infections caused by Gram-positive bacteria, such as Staphylococcus aureus and Bacillus anthracis
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Spivak, C.T.; Roseman, S.
UDP-N-acetyl-D-glucosamine 2'-epimerase
Methods Enzymol.
9
612-615
1966
Rattus norvegicus
-
brenda
Salo, W.L.; Fletcher, H.G.
Studies on the mechanism of action of uridine diphosphate N-acetylglucosamine 2-epimerase
Biochemistry
9
882-885
1970
Rattus norvegicus
brenda
Sommar, K.M.; Ellis, D.B.
Uridine diphosphate N-acetyl-D-glucosamine 2-epimerase from rat liver. I. Catalytic and regulatory properties
Biochim. Biophys. Acta
268
581-589
1972
Rattus norvegicus
brenda
Sommar, K.M.; Ellis, D.B.
Uridine diphosphate N-acetyl-D-glucosamine 2-epimerase from rat liver. II. Studies on the mechanism of action
Biochim. Biophys. Acta
268
590-595
1972
Rattus norvegicus
brenda
Kikuchi, K.; Tsuiki, S.
Purification and properties of UDP-N-acetylglucosamine 2'-epimerase from rat liver
Biochim. Biophys. Acta
327
193-206
1973
Rattus norvegicus
brenda
Kawamura, T.; Ichihara, N.; Ishimoto, N.; Ito, E.
Biosynthesis of uridine diphosphate N-acetyl-D-mannosaminuronic acid from uridine diphosphate N-acetyl-D-glucosamine in Escherichia coli: separation of enzymes responsible for epimerization and dehydrogenation
Biochem. Biophys. Res. Commun.
66
1506-1512
1975
Escherichia coli
brenda
Salo, W.L.
The incorporation of tritium from tritium-enriched water into UDP-N-acetylglucosamine and UDP-N-acetyl-mannosamine catalyzed by UDP-N-acetylglucosamine 2-epimerase from Escherichia coli
Biochim. Biophys. Acta
452
625-628
1976
Escherichia coli
brenda
Kawamura, T.; Kimura, M.; Yamamori, S.; Ito, E.
Enzymatic formation of uridine diphosphate N-acetyl-D-mannosamine
J. Biol. Chem.
253
3595-3601
1978
Bacillus cereus, Bacillus megaterium, Bacillus subtilis, Escherichia coli, Micrococcus luteus, Staphylococcus aureus
brenda
Kawamura, T.; Ishimoto, N.; Ito, E.
Enzymatic synthesis of uridine diphosphate N-acetyl-D-mannosaminuronic acid
J. Biol. Chem.
254
8457-8465
1979
Escherichia coli
brenda
Okubo, H.; Shibata, K.; Ishibashi, H.; Kudo, J.; Miyanaga, O.; Nagano, M.
Glucosamine-6-P synthetase and UDP-GlcNAc 2'-epimerase activities in tumor-bearing animals
Jpn. J. Clin. Chem.
8
99-103
1979
Rattus norvegicus
-
brenda
Kikuchi, K.; Tsuiki, S.
UDP-N-acetylglucosamine 2'-epimerase of rat hepatoma and its comparison with the enzyme of rat liver
Tohoku J. Exp. Med.
131
209-214
1980
Mus musculus, Rattus norvegicus
brenda
Kawamura, T.; Ishimoto, N.; Ito, E.
UDP-N-acetyl-D-glucosamine 2'-epimerase from Escherichia coli
Methods Enzymol.
83
515-519
1982
Escherichia coli
brenda
Van Rinsum, J.; van Dijk, W.; Hooghwinkel, G.J.M.; Ferwerda, W.
Subcellular localization and tissue distribution of sialic acid precursor-forming enzymes
Biochem. J.
210
21-28
1983
Rattus norvegicus
brenda
Corfield, A.P.; Clamp, J.R.; Wagner, S.A.
The metabolism of sialic acids in isolated rat colonic mucosal cells
Biochem. Soc. Trans.
11
767-768
1983
Rattus norvegicus
-
brenda
Harrington, C.R.; Baddiley, J.
Biosynthesis of wall teichoic acids in Staphylococcus aureus H, Micrococcus varians and Bacillus subtilis W23
Eur. J. Biochem.
153
639-645
1985
Kocuria varians, Staphylococcus aureus
brenda
Kawamura, T.; Ichihara, N.; Sugiyama, S.; Yokota, H.; Ishimoto, N.; Ito, E.
Biosynthesis of UDP-N-acetyl-D-glucosaminuronic acid and UDP-N-acetyl-D-mannosaminuronic acid in Micrococcus luteus
J. Biochem.
98
105-116
1985
Micrococcus luteus
brenda
Scocca, J.R.
Identification of N-acetylhexosamines produced by enzymes of the N-acetylneuraminic acid metabolic pathway by borate complex anion-exchange chromatography of the corresponding N-acetylhexosaminitols
Anal. Biochem.
156
61-66
1986
Homo sapiens
brenda
Sala, R.F.; Morgan, P.M.; Tanner, M.E.
Enzymic formation and release of a stable glycal intermediate: the mechanism of the reaction catalyzed by UDP-N-acetylglucosamine 2-epimerase
J. Am. Chem. Soc.
118
3033-3034
1996
Escherichia coli
-
brenda
Zeitler, R.; Banzer, J.P.; Bauer, C.; Reutter, W.
Inhibition of the biosynthesis of N-acetylneuraminic acid by metal ions and selenium in vitro
Biometals
5
103-109
1992
Rattus norvegicus
brenda
Gal, B.; Ruano, M.J.; Puente, R.; Garcia-Pardo, L.A.; Rueda, R.; Gil, A.; Hueso, P.
Developmental changes in UDP-N-acetylglucosamine 2-epimerase activity in rat and guinea-pig liver
Comp. Biochem. Physiol. B
118
13-15
1997
Cavia porcellus, Rattus norvegicus
brenda
Stäsche, R.; Hinderlich, S.; Weise, C.; Effertz, K.; Lucka, L.; Moormann, P.; Reutter, W.
A bifunctional enzyme catalyzes the first two steps in N-acetylneuraminic acid biosynthesis of rat liver. Molecular cloning and functional expression of UDP-N-acetyl-glucosamine 2-epimerase/N-acetylmannosamine kinase
J. Biol. Chem.
272
24319-24324
1997
Rattus norvegicus (O35826)
brenda
Hinderlich, S.; Stäsche, R.; Zeitler, R.; Reutter, W.
A bifunctional enzyme catalyzes the first two steps in N-acetylneuraminic acid biosynthesis of rat liver. Purification and characterization of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
J. Biol. Chem.
272
24313-24318
1997
Rattus norvegicus
brenda
Morgan, P.M.; Sala, R.F.; Tanner, M.E.
Elimination in the reactions catalyzed by UDP-N-acetylglucosamine 2-epimerase
J. Am. Chem. Soc.
119
10269-10277
1997
Escherichia coli
-
brenda
Corfield, A.P.; Hutton, C.W.; Clamp, J.R.; Dieppe, P.A.
Changes in sialic acid metabolism occur in colon and liver during the acute-phase response
Biochem. Soc. Trans.
14
628-629
1986
Rattus norvegicus
-
brenda
Corfield, A.P.; Rainey, J.B.; Clamp, J.R.; Wagner, S.A.
Changes in the activity of the enzymes involved in sialic acid metabolism in isolated rat colonic mucosal cells on administration of azoxymethane
Biochem. Soc. Trans.
11
766-767
1983
Rattus norvegicus
-
brenda
Effertz, K.; Hinderlich, S.; Reutter, W.
Selective loss of either the epimerase or kinase activity of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase due to site-directed mutagenesis based on sequence alignments
J. Biol. Chem.
274
28771-28778
1999
Rattus norvegicus
brenda
Lucka, L.; Krause, M.; Danker, K.; Reutter, W.; Horstkorte, R.
Primary structure and expression analysis of human UDP-N-acetyl-glucosamine-2-epimerase/N-acetylmannosamine kinase, the bifunctional enzyme in neuraminic acid biosynthesis
FEBS Lett.
454
341-344
1999
Homo sapiens (Q9Y223)
brenda
Sri Kannathasan, V.; Staines, A.G.; Dong, C.J.; Field, R.A.; Preston, A.G.; Maskell, D.J.; Naismith, J.H.
Overexpression, purification, crystallization and data collection on the Bordetella pertussis wlbD gene product, a putative UDP-GlcNAc 2'-epimerase
Acta Crystallogr. Sect. D
57
1310-1312
2001
Bordetella pertussis
brenda
Campbell, R.E.; Mosimann, S.C.; Tanner, M.E.; Strynadka, N.C.
The structure of UDP-N-acetylglucosamine 2-epimerase reveals homology to phosphoglycosyl transferases
Biochemistry
39
14993-15001
2000
Escherichia coli (P27828)
brenda
Blume, A.; Chen, H.; Reutter, W.; Schmidt, R.R.; Hinderlich, S.
2',3'-Dialdehydo-UDP-N-acetylglucosamine inhibits UDP-N-acetylglucosamine 2-epimerase, the key enzyme of sialic acid biosynthesis
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521
127-132
2002
Rattus norvegicus
brenda
Chou, W.K.; Hinderlich, S.; Reutter, W.; Tanner, M.E.
Sialic acid biosynthesis: stereochemistry and mechanism of the reaction catalyzed by the mammalian UDP-N-acetylglucosamine 2-epimerase
J. Am. Chem. Soc.
125
2455-2461
2003
Rattus norvegicus
brenda
Vann, W.F.; Daines, D.A.; Murkin, A.S.; Tanner, M.E.; Chaffin, D.O.; Rubens, C.E.; Vionnet, J.; Silver, R.P.
The NeuC protein of Escherichia coli K1 is a UDP N-acetylglucosamine 2-epimerase
J. Bacteriol.
186
706-712
2004
Escherichia coli, Escherichia coli K1
brenda
Stolz, F.; Reiner, M.; Blume, A.; Reutter, W.; Schmidt, R.R.
Novel UDP-glycal derivatives as transition state analogue inhibitors of UDP-GlcNAc 2-epimerase
J. Org. Chem.
69
665-679
2004
Rattus norvegicus
brenda
Keppler, O.T.; Hinderlich, S.; Langner, J.; Schwartz-Albiez, R.; Reutter, W.; Pawlita, M.
UDP-GlcNAc 2-epimerase: a regulator of cell surface sialylation
Science
284
1372-1376
1999
Homo sapiens
brenda
Blume, A.; Weidemann, W.; Stelzl, U.; Wanker, E.E.; Lucka, L.; Donner, P.; Reutter, W.; Horstkorte, R.; Hinderlich, S.
Domain-specific characteristics of the bifunctional key enzyme of sialic acid biosynthesis, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
Biochem. J.
384
599-607
2004
Rattus norvegicus
brenda
Murkin, A.S.; Chou, W.K.; Wakarchuk, W.W.; Tanner, M.E.
Identification and mechanism of a bacterial hydrolyzing UDP-N-acetylglucosamine 2-epimerase
Biochemistry
43
14290-14298
2004
Neisseria meningitidis
brenda
Samuel, J.; Tanner, M.E.
Active site mutants of the 'non-hydrolyzing' UDP-N-acetylglucosamine 2-epimerase from Escherichia coli
Biochim. Biophys. Acta
1700
85-91
2004
Escherichia coli
brenda
Krause, S.; Hinderlich, S.; Amsili, S.; Horstkorte, R.; Wiendl, H.; Argov, Z.; Mitrani-Rosenbaum, S.; Lochmueller, H.
Localization of UDP-GlcNAc 2-epimerase/ManAc kinase (GNE) in the Golgi complex and the nucleus of mammalian cells
Exp. Cell Res.
304
365-379
2005
Homo sapiens
brenda
Giordanengo, V.; Ollier, L.; Lanteri, M.; Lesimple, J.; March, D.; Thyss, S.; Lefebvre, J.C.
Epigenetic reprogramming of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) in HIV-1-infected CEM T cells
FASEB J.
18
1961-1963
2004
Homo sapiens (Q9Y223)
brenda
Hinderlich, S.; Salama, I.; Eisenberg, I.; Potikha, T.; Mantey, L.R.; Yarema, K.J.; Horstkorte, R.; Argov, Z.; Sadeh, M.; Reutter, W.; Mitrani-Rosenbaum, S.
The homozygous M712T mutation of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase results in reduced enzyme activities but not in altered overall cellular sialylation in hereditary inclusion body myopathy
FEBS Lett.
566
105-109
2004
Homo sapiens, Homo sapiens (Q9Y223)
brenda
Sparks, S.E.; Ciccone, C.; Lalor, M.; Orvisky, E.; Klootwijk, R.; Savelkoul, P.J.; Dalakas, M.C.; Krasnewich, D.M.; Gahl, W.A.; Huizing, M.
Use of a cell-free system to determine UDP-N-acetylglucosamine 2-epimerase and N-acetylmannosamine kinase activities in human hereditary inclusion body myopathy
Glycobiology
15
1102-1110
2005
Homo sapiens
brenda
Noguchi, S.; Keira, Y.; Murayama, K.; Ogawa, M.; Fujita, M.; Kawahara, G.; Oya, Y.; Imazawa, M.; Goto, Y.I.; Hayashi, Y.K.; Nonaka, I.; Nishino, I.
Reduction of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase activity and sialylation in distal myopathy with rimmed vacuoles
J. Biol. Chem.
279
11402-11407
2004
Homo sapiens
brenda
Blume, A.; Benie, A.J.; Stolz, F.; Schmidt, R.R.; Reutter, W.; Hinderlich, S.; Peters, T.
Characterization of ligand binding to the bifunctional key enzyme in the sialic acid biosynthesis by NMR: I. Investigation of the UDP-GlcNAc 2-epimerase functionality
J. Biol. Chem.
279
55715-55721
2004
Rattus norvegicus
brenda
Blume, A.; Ghaderi, D.; Liebich, V.; Hinderlich, S.; Donner, P.; Reutter, W.; Lucka, L.
UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, functionally expressed in and purified from Escherichia coli, yeast, and insect cells
Protein Expr. Purif.
35
387-396
2004
Rattus norvegicus
brenda
Penner, J.; Mantey, L.R.; Elgavish, S.; Ghaderi, D.; Cirak, S.; Berger, M.; Krause, S.; Lucka, L.; Voit, T.; Mitrani-Rosenbaum, S.; Hinderlich, S.
Influence of UDP-GlcNAc 2-epimerase/ManNAc kinase mutant proteins on hereditary inclusion body myopathy
Biochemistry
45
2968-2977
2006
Escherichia coli, Escherichia coli (P27828)
brenda
Reinke, S.O.; Hinderlich, S.
Prediction of three different isoforms of the human UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
FEBS Lett.
581
3327-3331
2007
Homo sapiens, Homo sapiens (Q9Y223), Mus musculus (Q3UW64)
brenda
Bork, K.; Reutter, W.; Weidemann, W.; Horstkorte, R.
Enhanced sialylation of EPO by overexpression of UDP-GlcNAc 2-epimerase/ManAc kinase containing a sialuria mutation in CHO cells
FEBS Lett.
581
4195-4198
2007
Rattus norvegicus
brenda
Gagiannis, D.; Orthmann, A.; Danssmann, I.; Schwarzkopf, M.; Weidemann, W.; Horstkorte, R.
Reduced sialylation status in UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE)-deficient mice
Glycoconj. J.
24
125-130
2007
Mus musculus
brenda
Wang, Z.; Sun, Z.; Li, A.V.; Yarema, K.J.
Roles for UDP-GlcNAc 2-epimerase/ManNAc 6-kinase outside of sialic acid biosynthesis: modulation of sialyltransferase and BiP expression, GM3 and GD3 biosynthesis, proliferation, and apoptosis, and ERK1/2 phosphorylation
J. Biol. Chem.
281
27016-27028
2006
Homo sapiens
brenda
Ghaderi, D.; Strauss, H.M.; Reinke, S.; Cirak, S.; Reutter, W.; Lucka, L.; Hinderlich, S.
Evidence for dynamic interplay of different oligomeric states of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase by biophysical methods
J. Mol. Biol.
369
746-758
2007
Rattus norvegicus
brenda
Castilho, A.; Pabst, M.; Leonard, R.; Veit, C.; Altmann, F.; Mach, L.; Gloessl, J.; Strasser, R.; Steinkellner, H.
Construction of a functional CMP-sialic acid biosynthesis pathway in Arabidopsis
Plant Physiol.
147
331-339
2008
Mus musculus
brenda
Velloso, L.M.; Bhaskaran, S.S.; Schuch, R.; Fischetti, V.A.; Stebbins, C.E.
A structural basis for the allosteric regulation of non-hydrolysing UDP-GlcNAc 2-epimerases. [Erratum to document cited in CA148:302197]
EMBO Rep.
9
1251
2008
Bacillus anthracis
-
brenda
Reinke, S.O.; Eidenschink, C.; Jay, C.M.; Hinderlich, S.
Biochemical characterization of human and murine isoforms of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE)
Glycoconj. J.
26
415-422
2009
Homo sapiens, Mus musculus
brenda
Namboori, S.C.; Graham, D.E.
Acetamido sugar biosynthesis in the Euryarchaea
J. Bacteriol.
190
2987-2996
2008
Methanococcus maripaludis (Q6LZC4)
brenda
Amsili, S.; Zer, H.; Hinderlich, S.; Krause, S.; Becker-Cohen, M.; MacArthur, D.G.; North, K.N.; Mitrani-Rosenbaum, S.
UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) binds to alpha-actinin 1: novel pathways in skeletal muscle?
PLoS ONE
3
e2477
2008
Homo sapiens
brenda
Reinke, S.O.; Lehmer, G.; Hinderlich, S.; Reutter, W.
Regulation and pathophysiological implications of UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) as the key enzyme of sialic acid biosynthesis
Biol. Chem.
390
591-599
2009
Homo sapiens, Mus musculus, Rattus norvegicus
brenda
Voermans, N.C.; Guillard, M.; Doedee, R.; Lammens, M.; Huizing, M.; Padberg, G.W.; Wevers, R.A.; van Engelen, B.G.; Lefeber, D.J.
Clinical features, lectin staining, and a novel GNE frameshift mutation in hereditary inclusion body myopathy
Clin. Neuropathol.
29
71-77
2010
Homo sapiens
brenda
Saechao, C.; Valles-Ayoub, Y.; Esfandiarifard, S.; Haghighatgoo, A.; No, D.; Shook, S.; Mendell, J.R.; Rosales-Quintero, X.; Felice, K.J.; Morel, C.F.; Pietruska, M.; Darvish, D.
Novel GNE mutations in hereditary inclusion body myopathy patients of non-Middle Eastern descent
Genet. Test. Mol. Biomarkers
14
157-162
2010
Homo sapiens
brenda
Weidemann, W.; Klukas, C.; Klein, A.; Simm, A.; Schreiber, F.; Horstkorte, R.
Lessons from GNE-deficient embryonic stem cells: sialic acid biosynthesis is involved in proliferation and gene expression
Glycobiology
20
107-117
2010
Mus musculus
brenda
Kurochkina, N.; Yardeni, T.; Huizing, M.
Molecular modeling of the bifunctional enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase and predictions of structural effects of mutations associated with HIBM and sialuria
Glycobiology
20
322-337
2010
Homo sapiens, Homo sapiens (Q9Y223)
brenda
Moeller, H.; Boehrsch, V.; Lucka, L.; Hackenberger, C.P.; Hinderlich, S.
Efficient metabolic oligosaccharide engineering of glycoproteins by UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) knock-down
Mol. Biosyst.
7
2245-2251
2011
Homo sapiens
brenda
Xu, Y.; Brenning, B.; Clifford, A.; Vollmer, D.; Bearss, J.; Jones, C.; McCarthy, V.; Shi, C.; Wolfe, B.; Aavula, B.; Warner, S.; Bearss, D.J.; McCullar, M.V.; Schuch, R.; Pelzek, A.; Bhaskaran, S.S.; Stebbins, C.E.; Goldberg, A.R.; Fischetti, V.A.; Vankayalapati, H.
Discovery of novel putative inhibitors of UDP-GlcNAc 2-epimerase as potent antibacterial agents
ACS Med. Chem. Lett.
4
1142-1147
2013
Bacillus anthracis (Q81K32), Staphylococcus aureus (Q9REV4), Staphylococcus aureus
brenda
Chen, S.C.; Huang, C.H.; Shin Yang, C.; Liu, J.S.; Kuan, S.M.; Chen, Y.
Crystal structures of the archaeal UDP-GlcNAc 2-epimerase from Methanocaldococcus jannaschii reveal a conformational change induced by UDP-GlcNAc
Proteins
82
1519-1526
2014
Methanocaldococcus jannaschii, Methanocaldococcus jannaschii (Q58899), Methanocaldococcus jannaschii DSM 2661 (Q58899)
brenda
Zhang, L.; Muthana, M.M.; Yu, H.; McArthur, J.B.; Qu, J.; Chen, X.
Characterizing non-hydrolyzing Neisseria meningitidis serogroup A UDP-N-acetylglucosamine (UDP-GlcNAc) 2-epimerase using UDP-N-acetylmannosamine (UDP-ManNAc) and derivatives
Carbohydr. Res.
419
18-28
2016
Neisseria meningitidis serogroup A / serotype 4A (A0A0U1RGY0), Neisseria meningitidis serogroup A / serotype 4A Z2491 (A0A0U1RGY0)
brenda
Wang, Y.T.; Missiakas, D.; Schneewind, O.
GneZ, a UDP-GlcNAc 2-epimerase, is required for S-layer assembly and vegetative growth of Bacillus anthracis
J. Bacteriol.
196
2969-2978
2014
Bacillus anthracis, Bacillus anthracis (Q81K32), Bacillus anthracis (Q81X16)
brenda
Chen, S.; Huang, C.; Shin Yang, C.; Liu, J.; Kuan, S.; Chen, Y.
Crystal structures of the archaeal UDP-GlcNAc 2-epimerase from Methanocaldococcus jannaschii reveal a conformational change induced by UDP-GlcNAc
Proteins
82
1519-1526
2014
Bacillus subtilis 168 (P39131), Bacillus subtilis, Bacillus subtilis (P39131), Methanocaldococcus jannaschii, Methanocaldococcus jannaschii (Q58899)
brenda
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