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Information on EC 2.7.7.23 - UDP-N-acetylglucosamine diphosphorylase and Organism(s) Homo sapiens

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EC Tree
IUBMB Comments
Part of the pathway for acetamido sugar biosynthesis in bacteria and archaea. The enzyme from several bacteria (e.g., Escherichia coli, Bacillus subtilis and Haemophilus influenzae) has been shown to be bifunctional and also to possess the activity of EC 2.3.1.157, glucosamine-1-phosphate N-acetyltransferase [3,4,6]. The enzyme from plants and animals is also active toward N-acetyl-alpha-D-galactosamine 1-phosphate (cf. EC 2.7.7.83, UDP-N-acetylgalactosamine diphosphorylase) [5,7], while the bacterial enzyme shows low activity toward that substrate .
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Homo sapiens
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Synonyms
udp-n-acetylglucosamine pyrophosphorylase, lmuap1, glmumtb, glcnac-1-p utase, spl29, udp-n-acetylglucosamine pyrophosphorylase (uap), udp-n-acetylglucosamine pyrophosphorylase 1, agx-1, n-acetylglucosamine 1-phosphate uridyltransferase, udp-n-acetylhexosamine pyrophosphorylase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
acetylglucosamine 1-phosphate uridylyltransferase
-
-
-
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AGX-1
UniProt
AGX2
-
identical sequence to AGX1 except a 17 amino acid insert at C-terminus, 8 times less active with N-acetyl-D-galactosamine 1-phosphate than with N-acetyl-D-glucosamine 1-phosphate
GlmU
-
-
-
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UDP-GlcNAc pyrophosphorylase
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-
-
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UDP-HexNAc pyrophosphorylase
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-
-
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UDP-N-acetylgalactosamine pyrophosphorylase
UniProt
UDP-N-acetylhexosamine pyrophosphorylase
UniProt
UDPacetylglucosamine pyrophosphorylase
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-
-
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uridine diphosphate-N-acetylglucosamine pyrophosphorylase
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-
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uridine diphosphoacetylglucosamine phosphorylase
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uridine diphosphoacetylglucosamine pyrophosphorylase
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-
-
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UTP:2-acetamido-2-deoxy-alpha-D-glucose-1-phosphate uridylyltransferase
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-
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Ydl103c protein
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-
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-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
nucleotidyl group transfer
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-
-
-
SYSTEMATIC NAME
IUBMB Comments
UTP:N-acetyl-alpha-D-glucosamine-1-phosphate uridylyltransferase
Part of the pathway for acetamido sugar biosynthesis in bacteria and archaea. The enzyme from several bacteria (e.g., Escherichia coli, Bacillus subtilis and Haemophilus influenzae) has been shown to be bifunctional and also to possess the activity of EC 2.3.1.157, glucosamine-1-phosphate N-acetyltransferase [3,4,6]. The enzyme from plants and animals is also active toward N-acetyl-alpha-D-galactosamine 1-phosphate (cf. EC 2.7.7.83, UDP-N-acetylgalactosamine diphosphorylase) [5,7], while the bacterial enzyme shows low activity toward that substrate [4].
CAS REGISTRY NUMBER
COMMENTARY hide
9023-06-7
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
diphosphate + UDP-glucose
UTP + D-glucose 1-phosphate
show the reaction diagram
-
-
-
-
r
diphosphate + UDP-N-acetyl-D-galactosamine
UTP + N-acetyl-alpha-D-galactosamine 1-phosphate
show the reaction diagram
-
2-3 times more active with N-acetyl-D-galactosamine 1-phosphate than with N-acetyl-D-glucosamine 1-phosphate, AGX2 8 times less active with N-acetyl-D-galactosamine 1-phosphate than with N-acetyl-D-glucosamine 1-phosphate
-
-
?
diphosphate + UDP-N-acetyl-D-glucosamine
UTP + N-acetyl-alpha-D-glucosamine 1-phosphate
show the reaction diagram
UTP + GalNAzMe-1-phosphate
diphosphate + UDP-GalNAzMe
show the reaction diagram
the reaction is catalyzed only by mutant F383A
-
-
?
UTP + N-acetyl-alpha-D-galactosamine 1-phosphate
diphosphate + UDP-N-acetyl-alpha-D-galactosamine
show the reaction diagram
reaction of EC 2.7.7.83
-
-
?
UTP + N-acetyl-alpha-D-galactosamine 1-phosphate
diphosphate + UDP-N-acetyl-D-galactosamine
show the reaction diagram
-
-
-
-
?
UTP + N-acetyl-alpha-D-glucosamine 1-phosphate
diphosphate + UDP-N-acetyl-alpha-D-glucosamine
show the reaction diagram
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
diphosphate + UDP-N-acetyl-D-glucosamine
UTP + N-acetyl-alpha-D-glucosamine 1-phosphate
show the reaction diagram
UTP + N-acetyl-alpha-D-galactosamine 1-phosphate
diphosphate + UDP-N-acetyl-alpha-D-galactosamine
show the reaction diagram
reaction of EC 2.7.7.83
-
-
?
UTP + N-acetyl-alpha-D-glucosamine 1-phosphate
diphosphate + UDP-N-acetyl-alpha-D-glucosamine
show the reaction diagram
-
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mg2+
required
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.38 - 1.3
N-acetyl-alpha-D-galactosamine 1-phosphate
0.7 - 2.2
UDP-N-acetyl-D-glucosamine
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
additional information
the human UAP1 gene encodes two different isoforms, named AGX1 and AGX2, with AGX1 being more abundant in testis and AGX2 in somatic tissues. AGX-1 is an UDP-N-acetylgalactosamine diphosphorylase, EC 2.7.7.83, and AGX-2 is an UDP-N-acetylglucosamine diphosphorylase, EC 2.7.7.23
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
the naturally occuring UAP1 A229T mutation is potentially pathogenic. The A229T mutation induces structural changes, leading to reduced thermal stability and activity of the mutant compared to wild-type
additional information
the human UAP1 gene encodes two different isoforms, named AGX1 and AGX2, with AGX1 being more abundant in testis and AGX2 in somatic tissues
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
UAP1_HUMAN
522
0
58769
Swiss-Prot
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
57000
-
SDS-PAGE, AGX1 expressed in Escherichia coli
64000
-
SDS-PAGE, AGX2 expressed in Escherichia coli
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinant detagged AGX1A229T in complex with UDP-GlcNAc, X-ray diffraction structure determination and analysis at 1.7 A resolution, molecular replacement using the published AGX1 structure (PDB ID 1JV1) as a search model
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A229T
naturally occuring enzyme AGX1 mutation, and site-directed mutagenesis, the A229T mutation causes a reduction of protein thermal stability compared to wild-type AGX1, and AGX1A229T has lower activity in producing UDP-GlcNA. In diploid organisms, haploinsufficiency is a phenomenon in which a single copy of a functional gene is not sufficient to produce the normal/wild-type phenotype. The patient is only heterozygous for the UAP1 A229T missense mutation. The UAP1 gene is potentially haploinsufficient and LoF intolerant, and the heterozygous UAP1 A229T mutation is potentially pathogenic. The recombinant mutant enzyme shows a reduction of the melting temperature (Tm) by approximately 5.3°C compared to wild-type. The A229T mutation induces structural changes. The R228-E44 interaction is abolished in the AGX1A229T structure caused by the position shift of R228. The pushing effect is likely due to the bulkier side chain of threonine compared to that of alanine. Along with the conformational change of the N-terminal domain in the AGX1A229T structure, is M218 shifted by 0.8 A away from R169, weakening the Q112-R169-M218 interaction
F383A
the mutant can use GalNAzMe-1-phosphate as substrate
F383G
the mutant cannot use GalNAzMe-1-phosphate as substrate
G111A
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very low activity
G222A
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traces of activity in forward and reverse reaction with N-acetyl-D-glucosamine 1-phosphate and N-acetyl-D-galactosamine 1-phosphate
G224A
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low activity in forward and reverse reaction with N-acetyl-D-glucosamine 1-phosphate and N-acetyl-D-galactosamine 1-phosphate
P220A
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only slight changes in activity with N-acetyl-D-glucosamine 1-phosphate and N-acetyl-D-galactosamine 1-phosphate
R115A
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slight changes in Km
Y227A
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only slight changes in activity with N-acetyl-D-glucosamine 1-phosphate and N-acetyl-D-galactosamine 1-phosphate
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
GST fusion protein from E. coli
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recombinant N-terminally GST-tagged wild-type and mutant AGX1 from Escherichia coli strain (DE3) pLysS by glutathione affinity chromatography, the tag is cleaved off by PreScission protease, followed by gel filtration, and ultrafiltration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
AGX1 and AGX 2 expressed in Escherichia coli as GST fusion protein
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AGX1 expressed in Escherichia coli as GST fusion protein
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expressed in Escherichia coli as GST fusion protein, complementation of Saccharomyces cerevisiae deficiency mutant, all recombinant enzymes found to be active
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expression in Escherichia coli
gene UAP1 encodes two different isoforms, named AGX1 and AGX2, recombinant expression of N-terminally GST-tagged wild-type and mutant AGX1 in Escherichia coli strain (DE3) pLysS
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Mio, T.; Yabe, T.; Arisawa, M.; Yamada-Okabe, H.
The eukaryotic UDP-N-acetylglucosamine pyrophosphorylases. Gene cloning, protein expression, and catalytic mechanism
J. Biol. Chem.
273
14392-14397
1998
Candida albicans (O74933), Candida albicans, Homo sapiens, Saccharomyces cerevisiae (P43123), Saccharomyces cerevisiae
Manually annotated by BRENDA team
Wang-Gillam, A.; Pastuszak, I.; Elbein, A.D.
A 17-amino acid insert changes UDP-N-acetylhexosamine pyrophosphorylase specificity from UDP-GalNAc to UDP-GlcNAc
J. Biol. Chem.
273
27055-27057
1998
Homo sapiens, Sus scrofa
Manually annotated by BRENDA team
Wang-Gillam, A.; Pastuszak, I.; Stewart, M.; Drake, R.R.; Elbein, A.D.
Identification and modification of the uridine-binding site of the UDP-GalNAc (GlcNAc) pyrophosphorylase
J. Biol. Chem.
275
1433-1438
2000
Homo sapiens
Manually annotated by BRENDA team
Urbaniak, M.D.; Collie, I.T.; Fang, W.; Aristotelous, T.; Eskilsson, S.; Raimi, O.G.; Harrison, J.; Navratilova, I.H.; Frearson, J.A.; van Aalten, D.M.; Ferguson, M.A.
A novel allosteric inhibitor of the uridine diphosphate N-acetylglucosamine pyrophosphorylase from Trypanosoma brucei
ACS Chem. Biol.
8
1981-1987
2013
Homo sapiens (Q16222), Homo sapiens, Trypanosoma brucei, Trypanosoma brucei brucei (Q386Q8), Trypanosoma brucei brucei 927 / 4 GUTat10.1 / TREU927 (Q386Q8)
Manually annotated by BRENDA team
Chen, X.; Raimi, O.G.; Ferenbach, A.T.; van Aalten, D.M.F.
A missense mutation in a patient with developmental delay affects the activity and structure of the hexosamine biosynthetic pathway enzyme AGX1
FEBS Lett.
595
110-122
2020
Homo sapiens (Q16222)
Manually annotated by BRENDA team
Debets, M.F.; Tastan, O.Y.; Wisnovsky, S.P.; Malaker, S.A.; Angelis, N.; Moeckl, L.K.R.; Choi, J.; Flynn, H.; Wagner, L.J.S.; Bineva-Todd, G.; Antonopoulos, A.; Cioce, A.; Browne, W.M.; Li, Z.; Briggs, D.C.; Douglas, H.L.; Hess, G.T.; Agbay, A.J.; Roustan, C.; Kjaer, S.; Haslam, S.M.; Snijders, A.P.; Bassik, M.C.; , M.
Metabolic precision labeling enables selective probing of O-linked N-acetylgalactosamine glycosylation
Proc. Natl. Acad. Sci. USA
117
25293-25301
2020
Homo sapiens (Q16222)
Manually annotated by BRENDA team