1fif
From Proteopedia
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N-ACETYLGALACTOSAMINE-SELECTIVE MUTANT OF MANNOSE-BINDING PROTEIN-A (QPDWG-HDRPY)
Overview
Efficient release of ligands from the Ca(2+)-dependent, carbohydrate-recognition domain (CRD) of the hepatic asialoglycoprotein, receptor at endosomal pH requires a small set of conserved amino acids, that includes a critical histidine residue. When these residues are, incorporated at corresponding positions in an homologous galactose-binding, derivative of serum mannose-binding protein, the pH dependence of ligand, binding becomes more like that of the receptor. The modified CRD displays, 40-fold preferential binding to N-acetylgalactosamine compared with, galactose, making it a good functional mimic of the asialoglycoprotein, receptor. In the crystal structure of the modified CRD bound to, N-acetylgalactosamine, the histidine (His(202)) contacts the 2-acetamido, methyl group and also participates in a network of interactions involving, Asp(212), Arg(216), and Tyr(218) that positions a water molecule in a, hydrogen bond with the sugar amide group. These interactions appear to, produce the preference for N-acetylgalactosamine over galactose and are, also likely to influence the pK(a) of His(202). Protonation of His(202), would disrupt its interaction with an asparagine that serves as a ligand, for Ca(2+) and sugar. The structure of the modified CRD without sugar, displays several different conformations that may represent structures of, intermediates in the release of Ca(2+) and sugar ligands caused by, protonation of His(202).
About this Structure
1FIF is a Single protein structure of sequence from Rattus norvegicus with CA and CL as ligands. Full crystallographic information is available from OCA.
Reference
Mechanism of pH-dependent N-acetylgalactosamine binding by a functional mimic of the hepatocyte asialoglycoprotein receptor., Feinberg H, Torgersen D, Drickamer K, Weis WI, J Biol Chem. 2000 Nov 10;275(45):35176-84. PMID:10931846
Page seeded by OCA on Tue Nov 20 14:56:54 2007
