5.1.3.14: UDP-N-acetylglucosamine 2-epimerase (non-hydrolysing)
This is an abbreviated version!
For detailed information about UDP-N-acetylglucosamine 2-epimerase (non-hydrolysing), go to the full flat file.
Word Map on EC 5.1.3.14
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5.1.3.14
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sialic
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myopathy
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hereditary
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rimmed
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sialylation
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vacuoles
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n-acetylneuraminic
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quadriceps
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sialuria
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glycoconjugates
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hyposialylation
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udp-n-acetylmannosamine
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nonaka
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neu5ac
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inclusion-body
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drug development
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cmp-neu5ac
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cmp-n-acetylneuraminic
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cmp-sialic
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medicine
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synthesis
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biotechnology
- 5.1.3.14
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sialic
- myopathy
- hereditary
-
rimmed
-
sialylation
- vacuoles
-
n-acetylneuraminic
-
quadriceps
- sialuria
- glycoconjugates
-
hyposialylation
- udp-n-acetylmannosamine
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nonaka
- neu5ac
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inclusion-body
- drug development
- cmp-neu5ac
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cmp-n-acetylneuraminic
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cmp-sialic
- medicine
- synthesis
- biotechnology
Reaction
Synonyms
bas5048, bas5117, Bs-epimerase, Cap5P, Epimerase, uridine diphosphoacetylglucosamine 2-, GNE, GNE/MNK, GNE1, GNE2, GneY, GneZ, His-rGNE, Mj-epimerase, MnaA, More, NeuC protein, NmSacA, non-hydrolyzing Neisseria meningitidis serogroup A UDP-GlcNAc 2-epimerase, non-hydrolyzing Neisseria meningitidis serogroup A UDP-N-acetylglucosamine 2-epimerase, non-hydrolyzing UDP-GlcNAc 2-epimerase, non-hydrolyzing UDP-N-acetylglucosamine 2-epimerase, non-hydrolyzing uridine 5'-diphosphate-N-acetylglucosamine 2-epimerase, SacA, teichoic acid 2-epimerase, UDP-GlcNAc 2'-epimerase, UDP-GlcNAc 2-epimerase, UDP-GlcNAc 2-epimerase/ManAc kinase, UDP-GlcNAc 2-epimerase/ManNAc kinase, UDP-GlcNAc 2-epimerase/ManNAc kinase gene, UDP-GlcNAc-2-epimerase, UDP-GlcNAc:UDP-ManNAc 2-epimerase, UDP-N-acetylglucosamine 2'-epimerase, UDP-N-acetylglucosamine 2-epimerase, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, UDP-N-acetylglucosamine-2-epimerase, UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase, uridine diphosphate N-acetylglucosamine 2-epimerase, Uridine diphosphate-N-acetylglucosamine-2'-epimerase, Uridine diphospho-N-acetylglucosamine 2'-epimerase, Uridine diphosphoacetylglucosamine 2'-epimerase, wecB, WTA 2-epimerase
ECTree
5.1.3.14 UDP-N-acetylglucosamine 2-epimerase (non-hydrolysing)Advanced search results
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results (Engineering
Engineering on EC 5.1.3.14 - UDP-N-acetylglucosamine 2-epimerase (non-hydrolysing)
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
D95N
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about 18000 fold decrease in turnover number for UDP-N-acetyl-D-glucosamine, not possible to obtain accurate kinetic constants
E117Q
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about 18000 fold decrease in turnover number for UDP-N-acetyl-D-glucosamine, not possible to obtain accurate kinetic constants
E131Q
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about 18000 fold decrease in turnover number for UDP-N-acetyl-D-glucosamine, not possible to obtain accurate kinetic constants
H213N
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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
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more than 100fold increase in KM-value for UDP-N-acetyl-D-glucosamine
A630T
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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
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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
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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
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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
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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
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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
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a naturally occuring missense mutation in exon 5 of the GNE gene of a patient with hereditary inclusion body myopathy
I472T
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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
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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
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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
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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
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a naturally occuring missense mutation in exon 3 of the GNE gene of a patient with hereditary inclusion body myopathy
R8X
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a naturally occuring nonsense mutation in exon 2 of the GNE gene of a patient with hereditary inclusion body myopathy
S615X
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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
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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
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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
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a naturally occuring nonsense mutation in exon 3 of the GNE gene of a patient with hereditary inclusion body myopathy
Y675H
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a naturally occuring missense mutation in exon 12 of the GNE gene of a patient with hereditary inclusion body myopathy
D100N
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no conversion of UDP-N-acetyl-D-glucosamine to UDP + N-acetyl-D-mannosamine
D131N
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no conversion of UDP-N-acetyl-D-glucosamine to UDP + N-acetyl-D-mannosamine, acetamidoglucal is released from the active site during catalysis
E122Q
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no conversion of UDP-N-acetyl-D-glucosamine to UDP + N-acetyl-D-mannosamine, acetamidoglucal is released from the active site during catalysis
D100N
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no conversion of UDP-N-acetyl-D-glucosamine to UDP + N-acetyl-D-mannosamine
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D131N
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no conversion of UDP-N-acetyl-D-glucosamine to UDP + N-acetyl-D-mannosamine, acetamidoglucal is released from the active site during catalysis
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E122Q
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no conversion of UDP-N-acetyl-D-glucosamine to UDP + N-acetyl-D-mannosamine, acetamidoglucal is released from the active site during catalysis
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D413K
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enzyme with mutation in the putative kinase active site shows drastic loss in their kinase activity but retains their epimerase activity
D413N
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enzyme with mutation in the putative kinase active site shows drastic loss in their kinase activity but retains their epimerase activity
H110A
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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
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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
H157A
R420M
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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 occuirng missense mutation the epimerase part of the bifunctional enzyme
R246Q
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a naturally occuring missense mutation in exon 4 of the GNE gene of a patient with hereditary inclusion body myopathy
R266Q
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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
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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 occuirng missense mutation the epimerase part of the bifunctional enzyme
R335W
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a naturally occuring missense mutation in exon 6 of the GNE gene of a patient with hereditary inclusion body myopathy
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
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a naturally occuring missense mutation in exon 12 of the GNE gene of a patient with hereditary inclusion body myopathy
V696M
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naturally occuring missense mutation G2086A involved in hereditary inclusion body myopathy, phenotype, overview
H155A
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mutant enzyme forms mainly trimeric enzyme with small amounts of hexamer
H155A
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mutant enzyme shows a drastic loss of epimerase activity, loss of epimerase activity can largely by attributed to incorrect protein folding
H157A
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mutant enzyme forms mainly trimeric enzyme with small amounts of hexamer
H157A
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mutant enzyme shows a drastic loss of epimerase activity, loss of epimerase activity can largely by attributed to incorrect protein folding
additional information
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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
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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
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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
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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
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the frame shif mutation 1295delA, leading to a premature stop codon at K432, is involved in hereditary inclusion body myopathy, phenotype, overview
additional information
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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
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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
additional information
gene mnaA, genotyping and mutation identification. Mapping of MnaA LOF mutations into the MnaA crystal structure revealing key residues for substrate binding site stability and charge. To determine whether L638R mnaA LOF mutants are not identified in MRSA COL due to a functional redundancy between Cap5P and MnaA, a cap5P deletion mutant is constructed and the L638R studies are repeated. Under these conditions, in addition to identifying the expected tarG L638R mutations as well as tarO and tarA LOF mutations, multiple (n = 11) independent resistor isolates obtained uniquely possess distinct mutations that map to mnaA and are predicted to inactivate gene function as well as directly confer L638R drug resistance based on the absence of additional non-synonymous mutations in their genome following WGS analysis. While MRSA COL DELTAcap5P exhibits no wall teichoic acid (WTA) depletion phenotype and remains resistant to beta-lactams, MRSA COL mnaA, DELTAcap5P double mutants are completely devoid of WTA and are also highly sensitive to beta-lactams. MRSA COL mnaA, cap5P double mutants and MRSE mnaA single mutants reveal morphological phenotypes consistent with WTA depletion, including increased cell size heterogeneity and septation defects. 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
additional information
gene mnaA, genotyping and mutation identification. Mapping of MnaA LOF mutations into the MnaA crystal structure revealing key residues for substrate binding site stability and charge. To determine whether L638R mnaA LOF mutants are not identified in MRSA COL due to a functional redundancy between Cap5P and MnaA, a cap5P deletion mutant is constructed and the L638R studies are repeated. Under these conditions, in addition to identifying the expected tarG L638R mutations as well as tarO and tarA LOF mutations, multiple (n = 11) independent resistor isolates obtained uniquely possess distinct mutations that map to mnaA and are predicted to inactivate gene function as well as directly confer L638R drug resistance based on the absence of additional non-synonymous mutations in their genome following WGS analysis. While MRSA COL DELTAcap5P exhibits no wall teichoic acid (WTA) depletion phenotype and remains resistant to beta-lactams, MRSA COL mnaA, DELTAcap5P double mutants are completely devoid of WTA and are also highly sensitive to beta-lactams. MRSA COL mnaA, cap5P double mutants and MRSE mnaA single mutants reveal morphological phenotypes consistent with WTA depletion, including increased cell size heterogeneity and septation defects. 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
additional information
-
gene mnaA, genotyping and mutation identification. Mapping of MnaA LOF mutations into the MnaA crystal structure revealing key residues for substrate binding site stability and charge. To determine whether L638R mnaA LOF mutants are not identified in MRSA COL due to a functional redundancy between Cap5P and MnaA, a cap5P deletion mutant is constructed and the L638R studies are repeated. Under these conditions, in addition to identifying the expected tarG L638R mutations as well as tarO and tarA LOF mutations, multiple (n = 11) independent resistor isolates obtained uniquely possess distinct mutations that map to mnaA and are predicted to inactivate gene function as well as directly confer L638R drug resistance based on the absence of additional non-synonymous mutations in their genome following WGS analysis. While MRSA COL DELTAcap5P exhibits no wall teichoic acid (WTA) depletion phenotype and remains resistant to beta-lactams, MRSA COL mnaA, DELTAcap5P double mutants are completely devoid of WTA and are also highly sensitive to beta-lactams. MRSA COL mnaA, cap5P double mutants and MRSE mnaA single mutants reveal morphological phenotypes consistent with WTA depletion, including increased cell size heterogeneity and septation defects. 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
additional information
to determine whether L638R mnaA LOF mutants are not identified in MRSA COL due to a functional redundancy between Cap5P and MnaA, a cap5P deletion mutant is constructed and the L638R studies are repeated. Under these conditions, in addition to identifying the expected tarG L638R mutations as well as tarO and tarA LOF mutations, multiple (n = 11) independent resistor isolates obtained uniquely possess distinct mutations that map to mnaA and are predicted to inactivate gene function as well as directly confer L638R drug resistance based on the absence of additional non-synonymous mutations in their genome following WGS analysis. While MRSA COL DELTAcap5P exhibits no wall teichoic acid (WTA) depletion phenotype and remains resistant to beta-lactams, MRSA COL mnaA, DELTAcap5P double mutants are completely devoid of WTA and are also highly sensitive to beta-lactams. MRSA COL mnaA, cap5P double mutants and MRSE mnaA single mutants reveal morphological phenotypes consistent with WTA depletion, including increased cell size heterogeneity and septation defects
additional information
to determine whether L638R mnaA LOF mutants are not identified in MRSA COL due to a functional redundancy between Cap5P and MnaA, a cap5P deletion mutant is constructed and the L638R studies are repeated. Under these conditions, in addition to identifying the expected tarG L638R mutations as well as tarO and tarA LOF mutations, multiple (n = 11) independent resistor isolates obtained uniquely possess distinct mutations that map to mnaA and are predicted to inactivate gene function as well as directly confer L638R drug resistance based on the absence of additional non-synonymous mutations in their genome following WGS analysis. While MRSA COL DELTAcap5P exhibits no wall teichoic acid (WTA) depletion phenotype and remains resistant to beta-lactams, MRSA COL mnaA, DELTAcap5P double mutants are completely devoid of WTA and are also highly sensitive to beta-lactams. MRSA COL mnaA, cap5P double mutants and MRSE mnaA single mutants reveal morphological phenotypes consistent with WTA depletion, including increased cell size heterogeneity and septation defects
additional information
-
to determine whether L638R mnaA LOF mutants are not identified in MRSA COL due to a functional redundancy between Cap5P and MnaA, a cap5P deletion mutant is constructed and the L638R studies are repeated. Under these conditions, in addition to identifying the expected tarG L638R mutations as well as tarO and tarA LOF mutations, multiple (n = 11) independent resistor isolates obtained uniquely possess distinct mutations that map to mnaA and are predicted to inactivate gene function as well as directly confer L638R drug resistance based on the absence of additional non-synonymous mutations in their genome following WGS analysis. While MRSA COL DELTAcap5P exhibits no wall teichoic acid (WTA) depletion phenotype and remains resistant to beta-lactams, MRSA COL mnaA, DELTAcap5P double mutants are completely devoid of WTA and are also highly sensitive to beta-lactams. MRSA COL mnaA, cap5P double mutants and MRSE mnaA single mutants reveal morphological phenotypes consistent with WTA depletion, including increased cell size heterogeneity and septation defects
additional information
-
to determine whether L638R mnaA LOF mutants are not identified in MRSA COL due to a functional redundancy between Cap5P and MnaA, a cap5P deletion mutant is constructed and the L638R studies are repeated. Under these conditions, in addition to identifying the expected tarG L638R mutations as well as tarO and tarA LOF mutations, multiple (n = 11) independent resistor isolates obtained uniquely possess distinct mutations that map to mnaA and are predicted to inactivate gene function as well as directly confer L638R drug resistance based on the absence of additional non-synonymous mutations in their genome following WGS analysis. While MRSA COL DELTAcap5P exhibits no wall teichoic acid (WTA) depletion phenotype and remains resistant to beta-lactams, MRSA COL mnaA, DELTAcap5P double mutants are completely devoid of WTA and are also highly sensitive to beta-lactams. MRSA COL mnaA, cap5P double mutants and MRSE mnaA single mutants reveal morphological phenotypes consistent with WTA depletion, including increased cell size heterogeneity and septation defects
-
additional information
-
gene mnaA, genotyping and mutation identification. Mapping of MnaA LOF mutations into the MnaA crystal structure revealing key residues for substrate binding site stability and charge. To determine whether L638R mnaA LOF mutants are not identified in MRSA COL due to a functional redundancy between Cap5P and MnaA, a cap5P deletion mutant is constructed and the L638R studies are repeated. Under these conditions, in addition to identifying the expected tarG L638R mutations as well as tarO and tarA LOF mutations, multiple (n = 11) independent resistor isolates obtained uniquely possess distinct mutations that map to mnaA and are predicted to inactivate gene function as well as directly confer L638R drug resistance based on the absence of additional non-synonymous mutations in their genome following WGS analysis. While MRSA COL DELTAcap5P exhibits no wall teichoic acid (WTA) depletion phenotype and remains resistant to beta-lactams, MRSA COL mnaA, DELTAcap5P double mutants are completely devoid of WTA and are also highly sensitive to beta-lactams. MRSA COL mnaA, cap5P double mutants and MRSE mnaA single mutants reveal morphological phenotypes consistent with WTA depletion, including increased cell size heterogeneity and septation defects. 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
-
additional information
-
gene mnaA, genotyping and mutation identification. MRSA COL mnaA, cap5P double mutants and MRSE mnaA single mutants reveal morphological phenotypes consistent with WTA depletion, including increased cell size heterogeneity and septation defects
additional information
Staphylococcus epidermidis CLB26329
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gene mnaA, genotyping and mutation identification. MRSA COL mnaA, cap5P double mutants and MRSE mnaA single mutants reveal morphological phenotypes consistent with WTA depletion, including increased cell size heterogeneity and septation defects
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