1FIH

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

1FIH の概要

• エントリーDOI: 10.2210/pdb1fih/pdb
• 関連するPDBエントリー: 1FIF
• 分子名称: MANNOSE-BINDING PROTEIN A, 2-acetamido-2-deoxy-beta-D-galactopyranose, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: lectin, c-type lectin, calcium-binding protein, sugar binding protein
• 由来する生物種: Rattus norvegicus (Norway rat)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 52908.23

構造登録者

Feinberg, H.,Torgerson, D.,Drickamer, K.,Weis, W.I. (登録日: 2000-08-03, 公開日: 2000-08-23, 最終更新日: 2024-10-30)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.95 Å)