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dihydropyrimidine-2,4(1H,3H)-dione-alpha-D-ribofuranosyl-5'-diphospho-2-acetamido-2-deoxy-alpha-D-mannopyranoside
?
N-Acetyl-D-glucosamine
?
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-
?
N-Acetyl-D-glucosamine 1-phosphate
?
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-
-
-
?
UDP-GlcNAc + H2O
ManNAc + UDP
-
biosynthesis of sialic acids
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-
?
UDP-N-acetyl-alpha-D-glucosamine
UDP-N-acetyl-alpha-D-mannosamine
UDP-N-acetyl-alpha-D-mannosamine
UDP-N-acetyl-alpha-D-glucosamine
UDP-N-acetyl-D-glucosamine
?
UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-D-mannosamine
UDP-N-acetyl-D-glucosamine + H2O
UDP + N-acetylmannosamine
UDP-N-acetylgalactosamine
?
-
-
-
-
?
uridine 5'-diphospho-2-hydroxyacetamido-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
-
-
-
?
additional information
?
-
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-GlcNAc
ManNAc + UDP
biosynthetic pathway of sialic acid
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-
?
UDP-GlcNAc
ManNAc + UDP
-
sialic acid biosynthetic pathway
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-
?
UDP-GlcNAc
ManNAc + UDP
-
biosynthesis of sialic acid
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-
?
UDP-N-acetyl-alpha-D-glucosamine
UDP-N-acetyl-alpha-D-mannosamine
Q81K32
-
-
-
r
UDP-N-acetyl-alpha-D-glucosamine
UDP-N-acetyl-alpha-D-mannosamine
Q81X16
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-
-
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
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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
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-
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
-
-
-
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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-
-
r
UDP-N-acetyl-alpha-D-glucosamine
UDP-N-acetyl-alpha-D-mannosamine
Neisseria meningitidis serogroup A / serotype 4A Z2491
-
-
-
r
UDP-N-acetyl-alpha-D-glucosamine
UDP-N-acetyl-alpha-D-mannosamine
Neisseria meningitidis serogroup A /serotype 4A
-
-
-
r
UDP-N-acetyl-alpha-D-glucosamine
UDP-N-acetyl-alpha-D-mannosamine
Neisseria meningitidis serogroup A /serotype 4A
interconversion
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-
r
UDP-N-acetyl-alpha-D-glucosamine
UDP-N-acetyl-alpha-D-mannosamine
Neisseria meningitidis serogroup A /serotype 4A Z2491
-
-
-
r
UDP-N-acetyl-alpha-D-glucosamine
UDP-N-acetyl-alpha-D-mannosamine
Neisseria meningitidis serogroup A /serotype 4A Z2491
interconversion
-
-
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
-
-
-
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
interconversion
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-
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
interconversion
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-
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
-
interconversion
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-
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
-
interconversion
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-
r
UDP-N-acetyl-alpha-D-mannosamine
UDP-N-acetyl-alpha-D-glucosamine
-
-
-
-
r
UDP-N-acetyl-alpha-D-mannosamine
UDP-N-acetyl-alpha-D-glucosamine
-
-
-
-
r
UDP-N-acetyl-alpha-D-mannosamine
UDP-N-acetyl-alpha-D-glucosamine
Neisseria meningitidis serogroup A / serotype 4A
-
-
-
r
UDP-N-acetyl-alpha-D-mannosamine
UDP-N-acetyl-alpha-D-glucosamine
Neisseria meningitidis serogroup A / serotype 4A Z2491
-
-
-
r
UDP-N-acetyl-alpha-D-mannosamine
UDP-N-acetyl-alpha-D-glucosamine
Neisseria meningitidis serogroup A /serotype 4A
interconversion
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-
r
UDP-N-acetyl-alpha-D-mannosamine
UDP-N-acetyl-alpha-D-glucosamine
Neisseria meningitidis serogroup A /serotype 4A Z2491
interconversion
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-
r
UDP-N-acetyl-alpha-D-mannosamine
UDP-N-acetyl-alpha-D-glucosamine
interconversion
-
-
r
UDP-N-acetyl-alpha-D-mannosamine
UDP-N-acetyl-alpha-D-glucosamine
interconversion
-
-
r
UDP-N-acetyl-alpha-D-mannosamine
UDP-N-acetyl-alpha-D-glucosamine
-
interconversion
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-
r
UDP-N-acetyl-alpha-D-mannosamine
UDP-N-acetyl-alpha-D-glucosamine
-
interconversion
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r
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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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
?
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?
UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-D-mannosamine
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non-hydrolizing
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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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?
UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-D-mannosamine
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-
-
?
UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-D-mannosamine
-
-
-
?
UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-D-mannosamine
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-
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r
UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-D-mannosamine
-
r
-
?
UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-D-mannosamine
-
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
-
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
-
the reverse reaction with UDP-N-acetylmannosamine requires the presence of UDP-N-acetylglucosamine
-
?
UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-D-mannosamine
-
-
-
?
UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-D-mannosamine
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-
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?
UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-D-mannosamine
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-
-
?
UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-D-mannosamine
-
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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-
r
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
-
-
-
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?
UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-D-mannosamine
-
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?
UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-D-mannosamine
-
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-
?
UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-D-mannosamine
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?
UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-D-mannosamine
-
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-
?
UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-D-mannosamine
-
reversibility is not detected
-
?
UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-D-mannosamine
-
reversibility is not detected
-
?
UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-D-mannosamine
-
key enzyme of sialic acid biosynthesis
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-
?
UDP-N-acetyl-D-glucosamine
UDP-N-acetyl-D-mannosamine
-
characterization of ligand binding to the bifunctional enzyme
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?
UDP-N-acetyl-D-glucosamine + H2O
UDP + N-acetylmannosamine
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?
UDP-N-acetyl-D-glucosamine + H2O
UDP + N-acetylmannosamine
-
-
-
?
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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?
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
-
-
-
-
?
uridine 5'-diphospho-2-hydroxyacetamido-2-deoxy-alpha-D-mannopyranoside
?
Neisseria meningitidis serogroup A / serotype 4A
-
-
-
?
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
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?
additional information
?
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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
?
-
-
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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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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biosynthesis of sialic acids
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?
additional information
?
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biosynthesis of sialic acids
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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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GNE is a bifunctional enzyme with UDP-GlcNAc 2-epimerase and ManNAc kinase activities
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?
additional information
?
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GNE is a bifunctional enzyme with UDP-GlcNAc 2-epimerase and ManNAc kinase activities
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?
additional information
?
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GNE is a bifunctional enzyme with UDP-GlcNAc 2-epimerase and ManNAc kinase activities
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?
additional information
?
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GNE is a bifunctional enzyme with UDP-GlcNAc 2-epimerase and ManNAc kinase activities
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-
?
additional information
?
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-
GNE is a bifunctional enzyme with UDP-GlcNAc 2-epimerase and ManNAc kinase activities
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-
?
additional information
?
-
biosynthesis of sialic acids
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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
?
-
-
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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-
GNE is a bifunctional enzyme with UDP-GlcNAc 2-epimerase and ManNAc kinase activities
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-
?
additional information
?
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-
GNE is a bifunctional enzyme with UDP-GlcNAc 2-epimerase and ManNAc kinase activities
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-
?
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
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?
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
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?
additional information
?
-
Neisseria meningitidis serogroup A /serotype 4A
the recombinnat enzyme His6-tagged NmSacA tolerates several chemoenzymatically synthesized UDP-ManNAc derivatives as substrates although its activity is much lower than with non-modified UDP-ManNAc, substrate specificity, overview
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?
additional information
?
-
Neisseria meningitidis serogroup A /serotype 4A Z2491
the recombinnat enzyme His6-tagged NmSacA tolerates several chemoenzymatically synthesized UDP-ManNAc derivatives as substrates although its activity is much lower than with non-modified UDP-ManNAc, substrate specificity, overview
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-
?
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
-
-
?