1nhe
Crystal structure of Lactose synthase complex with UDP
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OverviewOverview
The lactose synthase (LS) enzyme is a 1:1 complex of a catalytic, component, beta1,4-galactosyltransferse (beta4Gal-T1) and a regulatory, component, alpha-lactalbumin (LA), a mammary gland-specific protein. LA, promotes the binding of glucose (Glc) to beta4Gal-T1, thereby altering its, sugar acceptor specificity from N-acetylglucosamine (GlcNAc) to glucose, which enables LS to synthesize lactose, the major carbohydrate component, of milk. The crystal structures of LS bound with various substrates were, solved at 2 A resolution. These structures reveal that upon substrate, binding to beta4Gal-T1, a large conformational change occurs in the region, comprising residues 345 to 365. This repositions His347 in such a way that, it can participate in the coordination of a metal ion, and creates a sugar, and LA-binding site. At the sugar-acceptor binding site, a hydrophobic, N-acetyl group-binding pocket is found, formed by residues Arg359, Phe360, and Ile363. In the Glc-bound structure, this hydrophobic pocket is absent., For the binding of Glc to LS, a reorientation of the Arg359 side-chain, occurs, which blocks the hydrophobic pocket and maximizes the interactions, with the Glc molecule. Thus, the role of LA is to hold Glc by hydrogen, bonding with the O-1 hydroxyl group in the acceptor-binding site on, beta4Gal-T1, while the N-acetyl group-binding pocket in beta4Gal-T1, adjusts to maximize the interactions with the Glc molecule. This study, provides details of a structural basis for the partially ordered kinetic, mechanism proposed for lactose synthase.
About this StructureAbout this Structure
1NHE is a Protein complex structure of sequences from Bos taurus and Mus musculus with CA, UDP and PG4 as ligands. This structure superseeds the now removed PDB entry 1J94. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of lactose synthase reveals a large conformational change in its catalytic component, the beta1,4-galactosyltransferase-I., Ramakrishnan B, Qasba PK, J Mol Biol. 2001 Jun 29;310(1):205-18. PMID:11419947
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