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| [[Image:1fih.gif|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_1fih| PDB=1fih | SCENE= }} | | {{STRUCTURE_1fih| PDB=1fih | SCENE= }} |
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| '''N-ACETYLGALACTOSAMINE BINDING MUTANT OF MANNOSE-BINDING PROTEIN A (QPDWG-HDRPY), COMPLEX WITH N-ACETYLGALACTOSAMINE'''
| | ===N-ACETYLGALACTOSAMINE BINDING MUTANT OF MANNOSE-BINDING PROTEIN A (QPDWG-HDRPY), COMPLEX WITH N-ACETYLGALACTOSAMINE=== |
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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).
| | The line below this paragraph, {{ABSTRACT_PUBMED_10931846}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 10931846 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_10931846}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Calcium-binding protein]] | | [[Category: Calcium-binding protein]] |
| [[Category: Lectin]] | | [[Category: Lectin]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 16:22:03 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 03:19:19 2008'' |