Information on EC 2.3.1.45 - N-acetylneuraminate 7-O(or 9-O)-acetyltransferase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY hide
2.3.1.45
-
RECOMMENDED NAME
GeneOntology No.
N-acetylneuraminate 7-O(or 9-O)-acetyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
acetyl-CoA + N-acetylneuraminate = CoA + N-acetyl-7-O(or 9-O)-acetylneuraminate
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Acyl group transfer
SYSTEMATIC NAME
IUBMB Comments
acetyl-CoA:N-acetylneuraminate 7-O(or 9-O)-acetyltransferase
Both free and glycosidically bound N-acetyl- and N-glycolylneuraminates can act as O-acetyl acceptors.
CAS REGISTRY NUMBER
COMMENTARY hide
9054-50-6
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
the N-terminal domain of CASD1 differs from the canonical GDSL/SGNH fold by lacking the conserved residues G and N, and is therefore grouped into pfam family PF13839, i.e. GDSL/SGNH-like acylesterase family found in Pmr5 and Cas1p. While the N-terminal luminal domain of CASD1 displays the characteristic fold of an esterase39, it does not appear to function as such, no esterase activity with synthetic acetylesterase substrate 4-nitrophenylacetate nor towards natural O-acetylated sialoglycoconjugates
physiological function
CASD1 is a sialate O-acetyltransferase that catalyzes the transfer of acetyl groups from acetyl-coenzyme A to CMP-activated sialic acid and formation of a covalent acetyl-enzyme intermediate and serves as key enzyme in the biosynthesis of 9-O-acetylated sialoglycans
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + 5-N-acetylneuraminic acid
CoA + 5-N-acetyl-7-O-acetyl-neuraminate
show the reaction diagram
acetyl-CoA + 5-N-acetylneuraminic acid
CoA + 5-N-acetyl-8-O-acetyl-neuraminate
show the reaction diagram
acetyl-CoA + 5-N-acetylneuraminic acid
CoA + 5-N-acetyl-9-O-acetyl-neuraminate
show the reaction diagram
acetyl-CoA + alpha-2,3-sialyllactose
?
show the reaction diagram
-
-
-
-
?
acetyl-CoA + alpha-2,6-sialyllactose
?
show the reaction diagram
-
-
-
-
?
acetyl-CoA + CMP-5-N-acetylneuraminic acid
CoA + CMP-5-N-acetyl-7-O-acetyl-neuraminate
show the reaction diagram
acetyl-CoA + CMP-5-N-acetylneuraminic acid
CoA + CMP-5-N-acetyl-8-O-acetyl-neuraminate
show the reaction diagram
acetyl-CoA + CMP-5-N-acetylneuraminic acid
CoA + CMP-5-N-acetyl-9-O-acetyl-neuraminate
show the reaction diagram
acetyl-CoA + CMP-N-acetyl-neuraminate
CoA + CMP-9-O-acetyl-N-acetylneuraminate
show the reaction diagram
-
-
-
?
acetyl-CoA + CMP-N-acetylneuraminate
CoA + N-acetyl-9-O-acetylneuraminate + CMP
show the reaction diagram
acetyl-CoA + CMP-N-acetylneuraminic acid
CoA + CMP-N-acetyl-7-O-acetyl-neuraminate
show the reaction diagram
-
free acids or proteins as substrates
-
-
?
acetyl-CoA + CMP-N-acetylneuraminic acid
CoA + CMP-N-acetyl-7-O-acetylneuraminic acid
show the reaction diagram
-
-
-
-
?
acetyl-CoA + CMP-N-acetylneuraminic acid
CoA + CMP-N-acetyl-9-O-acetyl-neuraminate
show the reaction diagram
acetyl-CoA + colominic acid
CoA + ?
show the reaction diagram
-
-
-
-
?
acetyl-CoA + endogenous sialic acid
CoA + N-acetyl-7-O-acetylneuraminic acid
show the reaction diagram
-
-
-
-
?
acetyl-CoA + ganglioside GD3
CoA + ganglioside 9-O-acetyl-GD3
show the reaction diagram
-
-
-
-
?
acetyl-CoA + GD3 ganglioside
CoA + N-acetyl-9-O-acetylneuraminyl-GD3 ganglioside
show the reaction diagram
-
-
-
?
acetyl-CoA + N-acetylneuraminate
CoA + N-acetyl-7-O(or 9-O-)-acetylneuraminate
show the reaction diagram
acetyl-CoA + N-acetylneuraminate
CoA + N-acetyl-7-O-acetylneuraminate
show the reaction diagram
acetyl-CoA + N-acetylneuraminate
CoA + N-acetyl-9-O-acetylneuraminate
show the reaction diagram
-
-
-
-
?
acetyl-CoA + N-acetylneuraminic acid
CoA + N-acetyl-9-O-acetyl-neuraminate
show the reaction diagram
acetyl-CoA + N-acetylneuraminic acid
CoA + N-acetyl-O-acetyl-neuraminate
show the reaction diagram
acetyl-CoA + Neu5Acalpha2-8Neu5Acalpha2-3Galbeta1-4Glc-[6-(5-fluorescein-carboxamido)-hexanic acid succimidylester]
CoA + ?
show the reaction diagram
-
the O-acetylation reaction is also followed by real time NMR spectroscopy showing preferred incorporation of the acetyl group at C-9 of alpha2-8-linked Sia
-
-
?
acetyl-CoA + NeuAcalpha-2,3-Galbeta-1,4-Glc-6-(5-fluorescein-carboxamido)-hexanoic acid succimidyl ester
?
show the reaction diagram
the enzyme catalyzes the transfer of O-acetyl groups onto oligosaccharide-bound sialic acid, with a high specificity for terminal alpha2,8-linked residues, usage of 6-(5-fluorescein-carboxamido)-hexanoic acid succimidyl ester-labeled oligosaccharides
-
-
?
acetyl-CoA + NeuAcalpha-2,8-NeuAcalpha-2,3-Galbeta-1,4-Glc-6-(5-fluorescein-carboxamido)-hexanoic acid succimidyl ester
?
show the reaction diagram
the enzyme catalyzes the transfer of O-acetyl groups onto oligosaccharide-bound sialic acid, with a high specificity for terminal alpha2,8-linked residues, usage of 6-(5-fluorescein-carboxamido)-hexanoic acid succimidyl ester-labeled oligosaccharides
-
-
?
acetyl-CoA + NeuAcalpha-2,8-NeuAcalpha-2,8-NeuAcalpha-2,3-Galbeta-1,4-Glc-6-(5-fluorescein-carboxamido)-hexanoic acid succimidyl ester
?
show the reaction diagram
the enzyme catalyzes the transfer of O-acetyl groups onto oligosaccharide-bound sialic acid, with a high specificity for terminal alpha2,8-linked residues, usage of 6-(5-fluorescein-carboxamido)-hexanoic acid succimidyl ester-labeled oligosaccharides
-
-
?
acetyl-CoA + sialic acid
CoA + N-acetyl-7-O(or 9-O-)-acetylneuraminate
show the reaction diagram
CMP-N-acetylneuraminic acid + acetyl-CoA
CoA + CMP-5-N-acetyl-9-O-acetyl neuraminic acid
show the reaction diagram
-
-
-
-
?
N-acetylneuraminic acid + acetyl-CoA
CoA + 5-N-acetyl-9-O-acetyl neuraminic acid
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + 5-N-acetylneuraminic acid
CoA + 5-N-acetyl-7-O-acetyl-neuraminate
show the reaction diagram
acetyl-CoA + 5-N-acetylneuraminic acid
CoA + 5-N-acetyl-8-O-acetyl-neuraminate
show the reaction diagram
acetyl-CoA + 5-N-acetylneuraminic acid
CoA + 5-N-acetyl-9-O-acetyl-neuraminate
show the reaction diagram
acetyl-CoA + CMP-5-N-acetylneuraminic acid
CoA + CMP-5-N-acetyl-7-O-acetyl-neuraminate
show the reaction diagram
-
tissue- and cell type-specific modification of sialic acids, often in a development-dependent manner, plays a pivotal role in modulating various biological processes
-
-
?
acetyl-CoA + CMP-5-N-acetylneuraminic acid
CoA + CMP-5-N-acetyl-8-O-acetyl-neuraminate
show the reaction diagram
-
tissue- and cell type-specific modification of sialic acids, often in a development-dependent manner, plays a pivotal role in modulating various biological processes, e.g. terminal alpha2,8-linked sialic acid occurs on the glycerol side chain of GD3, where it reverses FAS-mediated apoptotic effects, suggesting a role of GD3 O-acetylation in regulating induced apoptosis, GD2 O-acetylation is oberseved in breast cancer
-
-
?
acetyl-CoA + CMP-5-N-acetylneuraminic acid
CoA + CMP-5-N-acetyl-9-O-acetyl-neuraminate
show the reaction diagram
-
tissue- and cell type-specific modification of sialic acids, often in a development-dependent manner, plays a pivotal role in modulating various biological processes, e.g. via 9-O-acetylation on colonic mucins, overview
-
-
?
acetyl-CoA + CMP-N-acetylneuraminate
CoA + N-acetyl-9-O-acetylneuraminate + CMP
show the reaction diagram
Q96PB1
-
-
-
?
acetyl-CoA + CMP-N-acetylneuraminic acid
CoA + CMP-N-acetyl-9-O-acetyl-neuraminate
show the reaction diagram
-
the CMP-N-acetyl-neuraminic acid and acetyl-CoA transporters are critical components for the O-acetylation of CMPNeu5Ac in Golgi lumen, with specific inhibition of either transporter leading to a reduction in the formation of CMP-5-N-acetyl-9-O-acetyl-neuraminic acid, O-acetylation in human colon Golgi vesicles is regulated by the concentration of CMP-Neu5Ac and AcCoA in the lumen, both being under the control of specific transport proteins, overview
-
-
?
acetyl-CoA + N-acetylneuraminate
CoA + N-acetyl-7-O-acetylneuraminate
show the reaction diagram
acetyl-CoA + N-acetylneuraminate
CoA + N-acetyl-9-O-acetylneuraminate
show the reaction diagram
-
-
-
-
?
acetyl-CoA + N-acetylneuraminic acid
CoA + N-acetyl-9-O-acetyl-neuraminate
show the reaction diagram
acetyl-CoA + N-acetylneuraminic acid
CoA + N-acetyl-O-acetyl-neuraminate
show the reaction diagram
acetyl-CoA + sialic acid
CoA + N-acetyl-7-O(or 9-O-)-acetylneuraminate
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
acetyl-CoA
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
EDTA
-
assay with 25 mM
KCl
-
activates, optimally at 50 mM for the solubilized enzyme and at 70 mM for the membrane-bound enzyme, 80% inhibition at 500 mM; optimum activity at 50 mM
additional information
-
the enzyme is not affected Mn2+, Ca2+, and Mg2+
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid
-
inhibition of O-acetylation in vivo through inhibition of Golgi substrate transporter proteins
coenzyme A
-
-
Cu2+
-
-
diethyl dicarbonate
iodoacetate
-
-
KCl
-
activates, optimally at 50 mM, 80% inhibition at 500 mM
methylamine
-
slightly
N-Acetylimidazole
-
-
N-bromosuccinimide
NaCl
-
50% inhibition at 50 mM
p-chloromercuribenzoate
-
-
Triton X-100
ZnCl2
-
50% inhibition at 1 mM
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-mercaptoethanol
-
slightly activates
acetic acid anhydride
-
activates
dithiothreitol
-
slightly activates
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0016 - 0.12
acetyl-CoA
0.059
CMP-5-N-acetyl-neuraminate
-
-
0.0592
CMP-5-N-acetylneuraminic acid
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pH 7.0, 37C
0.0073 - 0.1285
CMP-N-acetylneuraminic acid
0.5
N-acetylneuraminate
-
cytosolic enzyme
0.1385
N-acetylneuraminic acid
-
-
0.39
N-glycolylneuraminate
-
cytosolic enzyme
additional information
additional information
-
kinetics for the solubilized and the membrane-bound enzyme at different conditions, overview
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00074 - 0.56
CoA
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0004
purified recombinant enzyme, substrate monosialylated acceptor
0.0172
purified recombinant enzyme, substrate trisialylated acceptor
0.0778
purified recombinant enzyme, substrate disialylated acceptor
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.2
-
ELISA
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
-
activity assay; assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
a reduction of O-acetylation is associated with the early stages of colorectal cancer
Manually annotated by BRENDA team
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; from bone marrow
Manually annotated by BRENDA team
-
sialic acid O-acetylation levels in different samples, overview
Manually annotated by BRENDA team
additional information
-
high expression of O-acetylated GD3 occurs in human basalioma and melanoma
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
the enzyme is a multimembrane spanning protein with 13 transmembrane segments, the SGNH-like domain of CASD1 faces the Golgi lumen. The enzyme shows cytosolic and luminal orientation of its N- and C-terminus, respectively
Manually annotated by BRENDA team
-
7-O-acetylation
Manually annotated by BRENDA team
-
9-O-acetylation
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
115000
x * 115000, GFP-fusion protein, SDS-PAGE
150000 - 160000
-
gel filtration
150000
-
between 150000-160000 Da, determined by gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 115000, GFP-fusion protein, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
the soluble recombinant enzyme CASD1 expressed in Sf9 cells is N-glycosylated at the catalytic residue S94, the recombinant enzyme is therefore inactive
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22
-
50% loss of activity after 20 min at room temperature
37
-
activity is very labile
57
-
30 min, 75% loss of activity
additional information
-
the solubilised enzyme loses approximately 25% of its activity after 2 weeks at -20C. It is also stable at 48C for 8 h, but loses most of its activity at room temperature within a few hours
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
activity is stable to the first cycle of freezing, cannot be refrozen after thawing
-
enzyme is labile and difficult to solubilize
-
lyophilisation causes loss of 20-30% activity, storage in lyophilized stage leads to additional loss of 60% activity
-
Neu5Ac or CMP-Neu5Ac are strongly required for stabilization of the solubilized enzyme during purification
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, partially purified solubilized enzyme, 2 weeks, loss of 25% activity
-
-70C, prelabeled Golgi vesicles, 4 days
-
-80C, partially purified solubilized and membrane-bound enzyme, stable for several months
-
-80C, stable for several months
-
0C, 16 days, 55% loss of activity, membrane-bound enzyme
-
22C, room temperature, partially purified solubilized enzyme, almost complete loss of activity within a few hours
-
4C, partially purified solubilized enzyme, 8 h, quite stable
-
frozen enzyme is stable for at least 6 months
-
frozen Golgi vesicles are stable for 3-6 months
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
affinity purified
-
affinity purified; affinity-purified
-
native enzyme 53fold, partially, from microsomes by solubilization with the zwitterionic detergent CHAPS, i.e. 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonic acid, dialysis, anion exchange chromatography, and two steps of CoA affinity chromatography; using gel filtration, ion exchange chromatography, and affinity chromatography
-
recombinant enzyme from Escherichia coli strain AD202 by affinity chromatography
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cloning of cDNAs from melanoma genetic library that induce 9-O-acetylation of sialic acids, expression in COS cells
-
expressed in COS-7 cells, GFP-fusion protein expressed in Sf9 cells
gene neuD, DNA and amino acid sequence determination and analysis, phylogenetic analysis, homology modeling of NeuD
-
gene neuD, DNA and amino acid sequence determination and analysis, phylogenetic analysis, homology modeling of NeuD, functional complementation of an enzyme-deficient neuD-mutant Streptococcus sp. strain
orf11 gene, DNA and amino acid sequence determination and analysis, expression as soluble enzyme in Escherichia coli strain AD202
recombinant expression of N-terminally V5-tagged and C-terminally Myc-tagged enzyme in the murine fibroblast cell line LM-TK-, the enzyme co-localizes with the Golgi marker alpha-mannosidase II, and cytosolic and luminal orientation of N- and C-terminus, respectively, recombinant expression of a soluble secreted form of CASD1, which encompasses the SGNH-like luminal domain and a C-terminal Myc-His6-tag, in Spodoptera frugiperda SF9 cells via baculovirus transfection
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
in CD60b+ cells
sialate-O-acetyltransferase activity decreases with clinical remission
-
sialate-O-acetyltransferase activity increases at the diagnosis of leukemia, sharply increases again in relapsed patients
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
S94A
site-directed mutagenesis, inactive mutant
C88F
-
naturally occuring polymorphism
F88C
-
single nucleotide polymorphism, associated with variant group B streptococcal O-acetylation phenotype, overview
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
medicine
-
high level of SOAT activity in lymphoblasts of childhood acute lymphoblastic leukaemia (ALL) is detected. SOAT in cell lysates or microsomal fractions of lymphoblasts of patients is up to 22fold higher than in healthy donors. SOAT activity increases at the diagnosis of leukaemia, decreases with clinical remission and sharply increases again in relapsed patients as determined by radiometric-assay. A newly developed non-radioactive ELISA can quickly detect SOAT, and serves as tool for ALL-monitoring in larger scale