Summary for 1NF5
| Entry DOI | 10.2210/pdb1nf5/pdb |
| Descriptor | Alpha-lactalbumin, beta-1,4-galactosyltransferase, CALCIUM ION, ... (7 entities in total) |
| Functional Keywords | lactose synhtase, glucose binding, conformational change, transferase modulator, transferase-transferase complex, transferase/transferase |
| Biological source | Mus musculus (house mouse) More |
| Total number of polymer chains | 4 |
| Total formula weight | 94625.89 |
| Authors | Ramakrishnan, B.,Qasba, P.K. (deposition date: 2002-12-13, release date: 2002-12-25, Last modification date: 2020-07-29) |
| Primary citation | Ramakrishnan, B.,Qasba, P.K. Crystal Structure of Lactose Synthase Reveals a Large Conformational Change in its Catalytic Component, the beta-1,4-galactosyltransferase J.Mol.Biol., 310:205-218, 2001 Cited by PubMed Abstract: 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. PubMed: 11419947DOI: 10.1006/jmbi.2001.4757 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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