1fif
From Proteopedia
(New page: 200px<br /><applet load="1fif" size="450" color="white" frame="true" align="right" spinBox="true" caption="1fif, resolution 1.95Å" /> '''N-ACETYLGALACTOSAMIN...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1fif.gif|left|200px]]<br /><applet load="1fif" size=" | + | [[Image:1fif.gif|left|200px]]<br /><applet load="1fif" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1fif, resolution 1.95Å" /> | caption="1fif, resolution 1.95Å" /> | ||
'''N-ACETYLGALACTOSAMINE-SELECTIVE MUTANT OF MANNOSE-BINDING PROTEIN-A (QPDWG-HDRPY)'''<br /> | '''N-ACETYLGALACTOSAMINE-SELECTIVE MUTANT OF MANNOSE-BINDING PROTEIN-A (QPDWG-HDRPY)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Efficient release of ligands from the Ca(2+)-dependent | + | 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). |
==About this Structure== | ==About this Structure== | ||
| - | 1FIF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with CA and CL as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1FIF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=CL:'>CL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FIF OCA]. |
==Reference== | ==Reference== | ||
| Line 16: | Line 16: | ||
[[Category: Feinberg, H.]] | [[Category: Feinberg, H.]] | ||
[[Category: Torgersen, D.]] | [[Category: Torgersen, D.]] | ||
| - | [[Category: Weis, W | + | [[Category: Weis, W I.]] |
[[Category: CA]] | [[Category: CA]] | ||
[[Category: CL]] | [[Category: CL]] | ||
| Line 23: | Line 23: | ||
[[Category: lectin]] | [[Category: lectin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:38:58 2008'' |
Revision as of 10:39, 21 February 2008
|
N-ACETYLGALACTOSAMINE-SELECTIVE MUTANT OF MANNOSE-BINDING PROTEIN-A (QPDWG-HDRPY)
Overview
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).
About this Structure
1FIF is a Single protein structure of sequence from Rattus norvegicus with and as ligands. 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
Page seeded by OCA on Thu Feb 21 12:38:58 2008
