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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
45
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pubmed:dateCreated |
2000-11-27
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pubmed:databankReference |
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pubmed:abstractText |
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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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Acetylgalactosamine,
http://linkedlifedata.com/resource/pubmed/chemical/Amino Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Arginine,
http://linkedlifedata.com/resource/pubmed/chemical/Asialoglycoprotein Receptor,
http://linkedlifedata.com/resource/pubmed/chemical/Aspartic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Galactose,
http://linkedlifedata.com/resource/pubmed/chemical/Glycine,
http://linkedlifedata.com/resource/pubmed/chemical/Histidine,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/Water
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
275
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
35176-84
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:10931846-Acetylgalactosamine,
pubmed-meshheading:10931846-Amino Acids,
pubmed-meshheading:10931846-Arginine,
pubmed-meshheading:10931846-Asialoglycoprotein Receptor,
pubmed-meshheading:10931846-Aspartic Acid,
pubmed-meshheading:10931846-Calcium,
pubmed-meshheading:10931846-Carrier Proteins,
pubmed-meshheading:10931846-Crystallography, X-Ray,
pubmed-meshheading:10931846-Escherichia coli,
pubmed-meshheading:10931846-Galactose,
pubmed-meshheading:10931846-Glycine,
pubmed-meshheading:10931846-Histidine,
pubmed-meshheading:10931846-Hydrogen Bonding,
pubmed-meshheading:10931846-Hydrogen-Ion Concentration,
pubmed-meshheading:10931846-Kinetics,
pubmed-meshheading:10931846-Liver,
pubmed-meshheading:10931846-Models, Molecular,
pubmed-meshheading:10931846-Mutagenesis, Site-Directed,
pubmed-meshheading:10931846-Protein Binding,
pubmed-meshheading:10931846-Protein Conformation,
pubmed-meshheading:10931846-Receptors, Cell Surface,
pubmed-meshheading:10931846-Tyrosine,
pubmed-meshheading:10931846-Water
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pubmed:year |
2000
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pubmed:articleTitle |
Mechanism of pH-dependent N-acetylgalactosamine binding by a functional mimic of the hepatocyte asialoglycoprotein receptor.
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pubmed:affiliation |
Department of Structural Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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