Literature summary for 2.7.7.83 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 .

Search for more literature for 2.7.7.83

Cloned(Commentary)

Cloned (Comment)	Organism
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)

Crystallization (Comment)	Organism
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

Protein Variants	Comment	Organism
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

Metals/Ions	Comment	Organism	Structure
Mg2+	required	Homo sapiens

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q16222	-	-

Purification (Commentary)

Purification (Comment)	Organism
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

Source Tissue	Comment	Organism	Textmining
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	-
testis	-	Homo sapiens	-

Substrates and Products (Substrate)

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

Synonyms

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

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
7.5	-	assay at	Homo sapiens

General Information

General Information	Comment	Organism
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
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

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Release 2023.1 (January 2023)