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evolution
Q81K32
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
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
malfunction
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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
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GNE deficiency can lead to hereditary inclusion body myopathy, HIBM, phenotypes, overview
malfunction
GNE mutations can result in two human disorders, hereditary inclusion body myopathy, HIBM, and sialuria
malfunction
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inactivation of GNE causes early embryonic lethality
malfunction
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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
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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
deletions of early wall teichoic acid (WTA) biosynthetic enzymes are nonlethal, but cause diverse attenuated virulence phenotypes, deletions of later steps in WTA biosynthesis are not generally tolerated and the enzymes are normally essential for growth, an essential gene paradox. The beta-lactam antibiotic imipenem exhibits restored bactericidal activity against mnaA mutants in vitro and concomitant efficacy against 2-epimerase defective strains in a mouse thigh model of MRSA infection. Complementing DELTAcap5P mnaASa P12L and DELTAcap5P mnaASa Y194* with either cap5P or mnaASa reintroduced on an inducible plasmid restores WTA polymer levels, resistance to each of the beta-lactams tested, and wild-type sensitivity to L638
malfunction
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deletions of early wall teichoic acid (WTA) biosynthetic enzymes are nonlethal, but cause diverse attenuated virulence phenotypes, deletions of later steps in WTA biosynthesis are not generally tolerated and the enzymes are normally essential for growth, an essential gene paradox. The beta-lactam antibiotic imipenem exhibits restored bactericidal activity against mnaA mutants in vitro and concomitant efficacy against 2-epimerase defective strains in a mouse thigh model of MRSE infection
malfunction
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mutation of this enzyme causes changes in cell morphology and the thermoresistance of the cell wall
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malfunction
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deletions of early wall teichoic acid (WTA) biosynthetic enzymes are nonlethal, but cause diverse attenuated virulence phenotypes, deletions of later steps in WTA biosynthesis are not generally tolerated and the enzymes are normally essential for growth, an essential gene paradox. The beta-lactam antibiotic imipenem exhibits restored bactericidal activity against mnaA mutants in vitro and concomitant efficacy against 2-epimerase defective strains in a mouse thigh model of MRSA infection. Complementing DELTAcap5P mnaASa P12L and DELTAcap5P mnaASa Y194* with either cap5P or mnaASa reintroduced on an inducible plasmid restores WTA polymer levels, resistance to each of the beta-lactams tested, and wild-type sensitivity to L638
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malfunction
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deletions of early wall teichoic acid (WTA) biosynthetic enzymes are nonlethal, but cause diverse attenuated virulence phenotypes, deletions of later steps in WTA biosynthesis are not generally tolerated and the enzymes are normally essential for growth, an essential gene paradox. The beta-lactam antibiotic imipenem exhibits restored bactericidal activity against mnaA mutants in vitro and concomitant efficacy against 2-epimerase defective strains in a mouse thigh model of MRSE infection
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metabolism
GNE catalyzes the first two committed, rate-limiting steps in the biosynthesis of N-acetylneuraminic acid, i.e. sialic acid
metabolism
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GNE catalyzes the first two steps of sialic acid biosynthesis in the cytosol
metabolism
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GNE is the rate-limiting enzyme of N-acetylneuraminate, i.e. sialic acid, biosynthesis
metabolism
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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
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GNE is the key enzyme in the sialic acid biosynthetic pathway
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
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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
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physiological function
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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
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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
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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
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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
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
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
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
2-epimerase MnaA interconverts UDP-GlcNAc and UDP-ManNAc to modulate substrate levels of TarO and TarA wall teichoic acid (WTA) biosynthesis enzymes. Besides MnaA, Staphylococcus aureus maintains a second 2-epimerase involved in serotype 5 capsular polysaccharide (CP5) synthesis, Cap5P. MnaA and Cap5P provide compensatory WTA functional roles in Staphylococcus aureus. MnaA and other enzymes of WTA biosynthesis are required for biofilm formation in MRSA. Overlapping functional activity of MnaA and Cap5P in Staphylococci
physiological function
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2-epimerase MnaA interconverts UDP-GlcNAc and UDP-ManNAc to modulate substrate levels of TarO and TarA wall teichoic acid (WTA) biosynthesis enzymes. MnaA serves as the sole 2-epimerase required for WTA biosynthesis in Staphylococcus epidermidis. MnaA and other enzymes of WTA biosynthesis are required for biofilm formation in MRSE
physiological function
Neisseria meningitidis serogroup A /serotype 4A
Neisseria meningitidis serogroup A non-hydrolyzing UDP-GlcNAc 2-epimerase (NmSacA) catalyzes the interconversion between UDP-GlcNAc and uridine 5?-diphosphate-N-acetylmannosamine (UDP-ManNAc). It is a key enzyme involved in the biosynthesis of the capsular polysaccharide [-6ManNAc?1-phosphate-]n of N. meningitidis serogroup A, one of the six serogroups (A, B, C, W-135, X, and Y) that account for most cases of Neisseria meningitidis-caused bacterial septicemia and meningitis
physiological function
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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
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physiological function
Neisseria meningitidis serogroup A / serotype 4A Z2491
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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
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physiological function
Neisseria meningitidis serogroup A /serotype 4A Z2491
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Neisseria meningitidis serogroup A non-hydrolyzing UDP-GlcNAc 2-epimerase (NmSacA) catalyzes the interconversion between UDP-GlcNAc and uridine 5?-diphosphate-N-acetylmannosamine (UDP-ManNAc). It is a key enzyme involved in the biosynthesis of the capsular polysaccharide [-6ManNAc?1-phosphate-]n of N. meningitidis serogroup A, one of the six serogroups (A, B, C, W-135, X, and Y) that account for most cases of Neisseria meningitidis-caused bacterial septicemia and meningitis
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physiological function
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2-epimerase MnaA interconverts UDP-GlcNAc and UDP-ManNAc to modulate substrate levels of TarO and TarA wall teichoic acid (WTA) biosynthesis enzymes. Besides MnaA, Staphylococcus aureus maintains a second 2-epimerase involved in serotype 5 capsular polysaccharide (CP5) synthesis, Cap5P. MnaA and Cap5P provide compensatory WTA functional roles in Staphylococcus aureus. MnaA and other enzymes of WTA biosynthesis are required for biofilm formation in MRSA. Overlapping functional activity of MnaA and Cap5P in Staphylococci
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physiological function
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2-epimerase MnaA interconverts UDP-GlcNAc and UDP-ManNAc to modulate substrate levels of TarO and TarA wall teichoic acid (WTA) biosynthesis enzymes. MnaA serves as the sole 2-epimerase required for WTA biosynthesis in Staphylococcus epidermidis. MnaA and other enzymes of WTA biosynthesis are required for biofilm formation in MRSE
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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
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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
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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
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
Neisseria meningitidis serogroup A /serotype 4A
homology modeling and molecular docking reveal structural determinants of NmSacA substrate specificity. Disulfide bond formation is not required for the epimerase activity of NmSacA-His6
additional information
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comparison of the crystal structures of Methanocaldococcus jannaschii in open and closed conformations and of Bacillus subtilis. Homologous enzyme structure comparisons, overview
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additional information
Neisseria meningitidis serogroup A / serotype 4A Z2491
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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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additional information
Neisseria meningitidis serogroup A /serotype 4A Z2491
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homology modeling and molecular docking reveal structural determinants of NmSacA substrate specificity. Disulfide bond formation is not required for the epimerase activity of NmSacA-His6
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