Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary extracted from

  • 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 (2020), FEBS Lett., 595, 110-122 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.7.7.23 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 Homo sapiens
2.7.7.83 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 Homo sapiens

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
2.7.7.23 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 Homo sapiens
2.7.7.83 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 Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
2.7.7.23 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 Homo sapiens
2.7.7.83 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, M218 is shifted by 0.8 A away from R169, weakening the Q112-R169-M218 interaction Homo sapiens

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.7.7.23 Mg2+ required Homo sapiens
2.7.7.83 Mg2+ required Homo sapiens

Organism

EC Number Organism UniProt Comment Textmining
2.7.7.23 Homo sapiens Q16222
-
-
2.7.7.83 Homo sapiens Q16222
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
2.7.7.23 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 Homo sapiens
2.7.7.83 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 Homo sapiens

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.7.7.23 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 Homo sapiens
-
2.7.7.23 testis
-
 Homo sapiens
-
2.7.7.83 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 Homo sapiens
-
2.7.7.83 testis
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.7.23 UTP + N-acetyl-alpha-D-glucosamine 1-phosphate
-
 Homo sapiens diphosphate + UDP-N-acetyl-alpha-D-glucosamine
-
 ?
2.7.7.83 UTP + N-acetyl-alpha-D-glucosamine 1-phosphate AGX1 Homo sapiens diphosphate + UDP-N-acetyl-alpha-D-glucosamine
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.7.7.23 AGX-1 UniProt Homo sapiens
2.7.7.23 AGX1
-
 Homo sapiens
2.7.7.23 UAP1
-
 Homo sapiens
2.7.7.23 UDP-N-acetylgalactosamine pyrophosphorylase UniProt Homo sapiens
2.7.7.23 UDP-N-acetylhexosamine pyrophosphorylase UniProt Homo sapiens
2.7.7.83 AGX-1 UniProt Homo sapiens
2.7.7.83 AGX1
-
 Homo sapiens
2.7.7.83 UAP1
-
 Homo sapiens
2.7.7.83 UDP-N-acetylgalactosamine pyrophosphorylase UniProt Homo sapiens
2.7.7.83 UDP-N-acetylhexosamine pyrophosphorylase UniProt Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.7.7.23 7.5
-
 assay at Homo sapiens
2.7.7.83 7.5
-
 assay at Homo sapiens

General Information

EC Number General Information Comment Organism
2.7.7.23 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 Homo sapiens
2.7.7.23 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 Homo sapiens
2.7.7.83 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 Homo sapiens
2.7.7.83 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 Homo sapiens