1fih

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spinqualitylabelsall models PDB ID 1fih Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
, resolution 1.95Å
Ligands:	, and
Coordinates:	save as pdb, mmCIF, xml

N-ACETYLGALACTOSAMINE BINDING MUTANT OF MANNOSE-BINDING PROTEIN A (QPDWG-HDRPY), COMPLEX WITH N-ACETYLGALACTOSAMINE

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

1FIH is a Single protein structure of sequence from Rattus norvegicus. 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

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