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Literature summary extracted from

  • Qasba, P.K.; Ramakrishnan, B.; Boeggeman, E.
    Structure and function of beta-1,4-galactosyltransferase (2008), Curr. Drug Targets, 9, 292-309.
    View publication on PubMedView publication on EuropePMC

Activating Compound

EC Number Activating Compound Comment Organism Structure
2.4.1.38 alpha-lactalbumin modulates the enzyme's acceptor specificity, but does not interact with the sugar donor-binding site of beta4Gal-T1. Instead, interacting with the extended sugar-binding site of the closed conformer of beta4Gal-T1 in the enzyme-sugar nucleotide complex, lactalbumin stabilizes the complex, thereby facilitating the transfer of the sugar moiety from the less preferred sugar nucleotides to a monosaccharide, it kinetically enhances the transfer of the sugar residue from the less preferred sugar nucleotides to a monosaccharide, GlcNAc, lactalbumin binding site structure of beta4Gal-T family members, overview, modulation mechanism, overview Homo sapiens

Application

EC Number Application Comment Organism
2.4.1.38 drug development the enzyme is a target for rational design of specific inhibitors Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.4.1.38 expressed in NIH-3T3 cells Homo sapiens

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
2.4.1.38
-
Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
2.4.1.38 I289Y mutation of the Drosophila beta4GalNAc-T1 converts the enzyme to a beta-1,4-galactosyltransferase-1, beta4Gal-T1, by reducing its beta4GalNAc-T1 activity by nearly 1000fold while enhancing its beta4Gal-T1 activity by 80fold Drosophila melanogaster
2.4.1.38 M344H in the presence of Mg2+ the mutant exhibits 25% of the catalytic activity compared to the wild type enzyme in the presence of Mn2+. Although the mutant has higher Km in the presence of Mg2+ for the substrates compared to the wild type enzyme in the presence of Mn2+, the catalytic efficiency with respect to donor and acceptor has decreased by an order of about 13 and 6, respectively. The turnover number of the mutant is only reduced to 60% Homo sapiens
2.4.1.38 R228K the mutation enhances the glucosyltransferase activity of beta4GalNAc-T1, which is low for the wild-type enzyme, by steric alterations, overview Homo sapiens
2.4.1.38 R228LK the mutation enhances glucosyltransferase activity Homo sapiens
2.4.1.38 Y289I the mutation makes the enzyme equally as efficient as Gal- or GalNAc-transferase Homo sapiens
2.4.1.38 Y289L mutation of the beta4GalNAc-T1 converts the enzyme to a beta-1,4-galactosyltransferase-1, beta4Gal-T1. Substituting Tyr289 for Leu removes this restriction and the Tyr289Leu mutant can now transfer GalNAc or other Gal C2-analogues from their respective UDPderivatives, not normally substrates of the enzyme, to the acceptor GlcNAc with the same efficiency with which the wild-type enzyme transfers Gal from UDP-Gal, phenotype, overview Homo sapiens
2.4.1.38 Y289L the mutation makes the enzyme equally as efficient as Gal- or GalNAc-transferase Homo sapiens
2.4.1.38 Y289N the mutation makes the enzyme equally as efficient as Gal- or GalNAc-transferase Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.4.1.38 additional information structural features for rational design of specific inhibitors, overview Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.4.1.38 additional information
-
additional information
-
Drosophila melanogaster

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
2.4.1.38 Golgi membrane beta4Gal-T1 is a trans-Golgi glycosyltransferase, Glyco-T, with a type II membrane protein topology, a short N-terminal cytoplasmic domain, a membrane-spanning region, as well as a stem and a C-terminal catalytic domain facing the trans-Golgi-lumen Homo sapiens 139
-
2.4.1.38 membrane trans-membrane protein Homo sapiens 16020
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.4.1.38 Mn2+ required Homo sapiens
2.4.1.38 Mn2+ the catalytic domain has two flexible loops, a long and a small one, with the primary metal binding site being located at the N-terminal hinge region of the long flexible loop Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.4.1.38 additional information Homo sapiens beta-1,4-galactosylransferase participates in the synthesis of Galbeta1-4-GlcNac disaccharide unit of glycoconjugates, overview ?
-
?
2.4.1.38 additional information Homo sapiens beta4Gal-T1 participates in the synthesis of Galbeta1-4-GlcNac disaccharide unit of glycoconjugates ?
-
?

Organism

EC Number Organism UniProt Comment Textmining
2.4.1.38 Drosophila melanogaster
-
-
-
2.4.1.38 Homo sapiens
-
-
-

Reaction

EC Number Reaction Comment Organism Reaction ID
2.4.1.38 UDP-alpha-D-galactose + N-acetyl-beta-D-glucosaminylglycopeptide = UDP + beta-D-galactosyl-(1->4)-N-acetyl-beta-D-glucosaminylglycopeptide reaction mechanism, structure-function relationship, upon binding of metal ion and sugar-nucleotide, the flexible loops undergo a marked conformational change, from an open to a closed conformation. Conformational change simultaneously creates at the C-terminal region of the flexible loop an oligosaccharide acceptor binding site that did not exist before. The loop acts as a lid covering the bound donor substrate. After completion of the transfer of the glycosyl unit to the acceptor, the saccharide product is ejected and the loop reverts to its native conformation to release the remaining nucleotide moiety Homo sapiens

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.4.1.38 keratinocyte
-
Homo sapiens
-
2.4.1.38 lung cancer cell
-
Homo sapiens
-
2.4.1.38 RHEK-1 cell
-
Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.4.1.38 additional information beta-1,4-galactosylransferase participates in the synthesis of Galbeta1-4-GlcNac disaccharide unit of glycoconjugates, overview Homo sapiens ?
-
?
2.4.1.38 additional information an enzyme orthologue involved in the synthesis of glycoproteins and glycolipids, the sugar donor specificity of the enzyme toward galactose is determined by the Ile residue at position 289 in the binding pocket. The two proteins beta4Gal-T1 and alpha-lactalbukin crystallize together as a complex only in the presence of either donor substrate or acceptor Glc or GlcNAc to form lactose synthase. The specificity of the sugar donor is generally determined by a few residues in the sugar-nucleotide binding pocket. The conformational change in beta4Gal-T1 also creates the binding site for a mammary gland-specific protein, alpha-lactalbumin, which changes the acceptor specificity of the enzyme toward glucose to synthesize lactose during lactation Drosophila melanogaster ?
-
?
2.4.1.38 additional information beta4Gal-T1 participates in the synthesis of Galbeta1-4-GlcNac disaccharide unit of glycoconjugates Homo sapiens ?
-
?
2.4.1.38 UDP-galactose + N-acetyl-beta-D-glucosaminylglycopeptide for the binding of GlcNAc in the monosaccharide binding site of beta4Gal-T1, there is a hydrophobic N-acetyl group-binding pocket formed by residues Arg359, Phe360, and Ile363 from the ?-helix region in the closed conformation of the long loop, the sugar donor specificity of beta4Gal-T1 toward galactose is determined by the Tyr residue at position 289 in the binding pocket. The two proteins beta4Gal-T1 and alpha-lactalbukin crystallize together as a complex only in the presence of either donor substrate or acceptor Glc or GlcNAc to form lactose synthase. The specificity of the sugar donor is generally determined by a few residues in the sugar-nucleotide binding pocket. The conformational change in beta4Gal-T1 also creates the binding site for a mammary gland-specific protein, alpha-lactalbumin, which changes the acceptor specificity of the enzyme toward glucose to synthesize lactose during lactation Homo sapiens UDP + beta-D-galactosyl-(1-4)-N-acetyl-beta-D-glucosaminylglycopeptide
-
?

Subunits

EC Number Subunits Comment Organism
2.4.1.38 More beta4Gal-T1 is a trans-Golgi glycosyltransferase, Glyco-T, with a type II membrane protein topology, a short N-terminal cytoplasmic domain, a membrane-spanning region, as well as a stem and a C-terminal catalytic domain facing the trans-Golgi-lumen. The two proteins beta4Gal-T1 and alpha-lactalbukin crystallize together as a complex only in the presence of either donor substrate or acceptor Glc or GlcNAc to form lactose synthase Homo sapiens

Synonyms

EC Number Synonyms Comment Organism
2.4.1.38 beta-1,4-galactosyltransferase
-
Drosophila melanogaster
2.4.1.38 beta-1,4-galactosyltransferase
-
Homo sapiens
2.4.1.38 beta4Gal-T1
-
Drosophila melanogaster
2.4.1.38 beta4Gal-T1
-
Homo sapiens

General Information

EC Number General Information Comment Organism
2.4.1.38 physiological function beta4Gal-T1 interacts with alpha-lactalbumin to form the lactose synthase complex that transfers galactose from UDP-alpha-D-Gal to glucose, producing the lactose secreted in milk Homo sapiens