The lactose synthase acceptor site: a structural map derived from acceptor studies.
A pictorial map of the lactose synthase (galactosyl transferase) acceptor binding site has been formulated from this and published studies on substrate analogs and inhibitors. The basic requirements are a pyranose, thiopyranose or inositol ring structure and equatorial substituents (if any) at C-2, C-3, C-4, and C-5. The aglycone (at C-1) may be either alpha or beta-, but alpha- is somewhat preferred. In the absence of alpha-lactalbumin galactosyl transferase will accept long chain 2-N-acyl substituents on the glucosamine (GlcNH2) structure. An equatorial amino or N-acetyl substituent (e.g. mannosamine, N-acetylmannosamine) is also a suitable acceptor in the absence of alpha-lactalbumin since both N-acetylglucosamine and N-acetylmannosamine have complementary binding loci for the N-acyl moiety. The aglycone moiety must be equatorial (beta-configuration). However, upon alpha-lactalbumin binding the aglycone specificity allows for axial (alpha-configuration) as well as equatorial substituents. Furthermore, the 2-N-acyl substituent binding locus is blocked beyond a 2-N-hexanoyl group. It is suggested that alpha-lactalbumin binds to a hydrophobic site some distance from the C-2 group.
D000117:Acetylglucosamine / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D050260:Carbohydrate Metabolism; D002417:Cattle; D005944:Glucosamine / Q000031:analogs & derivatives*; D005947:Glucose / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism; D007768:Lactalbumin / Q000378:metabolism; D007788:Lactose Synthase / Q000378:metabolism*; D008968:Molecular Conformation; D009237:N-Acetyllactosamine Synthase / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D006023:Glycoproteins; D007768:Lactalbumin; D007788:Lactose Synthase; D009237:N-Acetyllactosamine Synthase; D005947:Glucose; D005944:Glucosamine; D000117:Acetylglucosamine