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1fif

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{{STRUCTURE_1fif| PDB=1fif | SCENE= }}
{{STRUCTURE_1fif| PDB=1fif | SCENE= }}
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'''N-ACETYLGALACTOSAMINE-SELECTIVE MUTANT OF MANNOSE-BINDING PROTEIN-A (QPDWG-HDRPY)'''
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===N-ACETYLGALACTOSAMINE-SELECTIVE MUTANT OF MANNOSE-BINDING PROTEIN-A (QPDWG-HDRPY)===
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==Overview==
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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).
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(as it appears on PubMed at http://www.pubmed.gov), where 10931846 is the PubMed ID number.
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{{ABSTRACT_PUBMED_10931846}}
==About this Structure==
==About this Structure==
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[[Category: Calcium-binding protein]]
[[Category: Calcium-binding protein]]
[[Category: Lectin]]
[[Category: Lectin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 03:19:06 2008''

Revision as of 00:19, 1 July 2008

Template:STRUCTURE 1fif

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

Template:ABSTRACT PUBMED 10931846

About this Structure

1FIF 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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