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PDBsum entry 1fif
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Sugar binding protein
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PDB id
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1fif
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Mechanism of ph-Dependent n-Acetylgalactosamine binding by a functional mimic of the hepatocyte asialoglycoprotein receptor.
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Authors
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H.Feinberg,
D.Torgersen,
K.Drickamer,
W.I.Weis.
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Ref.
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J Biol Chem, 2000,
275,
35176-35184.
[DOI no: ]
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PubMed id
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Abstract
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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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Figure 2.
Fig. 2. Coordination in the principal Ca^2+ site of
QPDWG-HDRPY. Carbon, nitrogen, oxygen, and calcium are
represented as white, blue, red, and green spheres,
respectively. Hydrogen bonds are shown as dashed black lines,
and Ca^2+ coordination bonds are solid green lines. a, GalNAc
complex, copy A. b, native, copy A. c, native, copy C. The two
alternate conformations of Asn210 are shown. d, native, copy B.
e, stereo view of superimposed copy A of the GalNAc complex
(white bonds) and native copy B (yellow bonds). f, schematic
drawing of the 8-coordinate Ca^2+ site in native copy A. g,
schematic drawing of the rearranged, 7-coordinate Ca^2+ site in
native copy B. The diagrams in f and g are in approximately the
same orientation shown in b and d, respectively, and emphasize
the rotation of the pentagonal equatorial coordination plane.
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Figure 4.
Fig. 4. Conformational differences around the principal
Ca^2+ site. The color scheme is the same as in Fig. 1a. Ca^2+ 1
and 2 are the auxiliary and principal sites, respectively. a,
native QPDWG-HDRPY, copy A. b, native QPDWG-HDRPY, copy B. c,
copy B of apo-MBP-C (23). d, superposition of QPDWG-HDRPY copy A
(blue), QPDWG-HDRPY copy B (red), and apo-MBP-C copy B (green).
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2000,
275,
35176-35184)
copyright 2000.
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