1FIF

N-ACETYLGALACTOSAMINE-SELECTIVE MUTANT OF MANNOSE-BINDING PROTEIN-A (QPDWG-HDRPY)

Summary for 1FIF

• Entry DOI: 10.2210/pdb1fif/pdb
• Related: 1FIH
• Descriptor: MANNOSE-BINDING PROTEIN-A, CALCIUM ION, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: lectin, c-type lectin, calcium-binding protein, sugar binding protein
• Biological source: Rattus norvegicus (Norway rat)
• Cellular location: Secreted : P19999
• Total number of polymer chains: 3
• Total formula weight: 51987.95

Authors

Feinberg, H.,Torgersen, D.,Drickamer, K.,Weis, W.I. (deposition date: 2000-08-03, release date: 2000-08-23, Last modification date: 2021-11-03)

Primary citation

Feinberg, H.,Torgersen, D.,Drickamer, K.,Weis, W.I.
Mechanism of pH-dependent N-acetylgalactosamine binding by a functional mimic of the hepatocyte asialoglycoprotein receptor.
J.Biol.Chem., 275:35176-35184, 2000

PubMed Abstract: 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).

PubMed: 10931846
DOI: 10.1074/jbc.M005557200

Experimental method

X-RAY DIFFRACTION (1.95 Å)