PDBsum entry 1afb

Lectin

PDB id: 1afb

Contents

Protein chains

154 a.a. *

Ligands

NGA ×3

Metals

_CL ×2

_CA ×9

Waters ×371

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Structural basis of galactose recognition by c-Type animal lectins.

Authors

A.R.Kolatkar, W.I.Weis.

Ref.

J Biol Chem, 1996, 271, 6679-6685.

PubMed id

8636086

Note In the PDB file this reference is annotated as "TO BE PUBLISHED". The citation details given above were identified by an automated search of PubMed on title and author names, giving a percentage match of 92%.

Abstract

The asialoglycoprotein receptors and many other C-type (Ca2+-dependent) animal lectins specifically recognize galactose- or N-acetylgalactosamine-terminated oligosaccharides. Analogous binding specificity can be engineered into the homologous rat mannose-binding protein A by changing three amino acids and inserting a glycine-rich loop (Iobst, S. T., and Drickamer, K. (1994) J. Biol. Chem. 269, 15512-15519). Crystal structures of this mutant complexed with beta-methyl galactoside and N-acetylgalactosamine (GalNAc) reveal that as with wild-type mannose-binding proteins, the 3- and 4-OH groups of the sugar directly coordinate Ca2+ and form hydrogen bonds with amino acids that also serve as Ca2+ ligands. The different stereochemistry of the 3- and 4-OH groups in mannose and galactose, combined with a fixed Ca2+ coordination geometry, leads to different pyranose ring locations in the two cases. The glycine-rich loop provides selectivity against mannose by holding a critical tryptophan in a position optimal for packing with the apolar face of galactose but incompatible with mannose binding. The 2-acetamido substituent of GalNAc is in the vicinity of amino acid positions identified by site-directed mutagenesis (Iobst, S. T., and Drickamer, K. (1996) J. Biol. Chem. 271, 6686-6693) as being important for the formation of a GalNAc-selective binding site.

Secondary reference #1

Title

Trimeric structure of a c-Type mannose-Binding protein.

Authors

W.I.Weis, K.Drickamer.

Ref.

Structure, 1994, 2, 1227-1240. [DOI no: 10.1016/S0969-2126(94)00124-3]

PubMed id

7704532

Figure 7.
Figure 7. A portion of the neck–CRD interface, shown with the 1.25σ contour of the final 2F[o]–F[c] map. Conserved hydrophobic residues are labeled; the residues come from the protomer whose number precedes the amino acid name. Figure 7. A portion of the neck–CRD interface, shown with the 1.25σ contour of the final 2F[o]–F[c] map. Conserved hydrophobic residues are labeled; the residues come from the protomer whose number precedes the amino acid name.

Figure 8.
Figure 8. Representative sequences of the neck region and portions of the CRDs following the last Gly-X-Y repeat taken from various subgroups of collectins. RA, rat; HU, human. The a and d positions of the heptadrepeats are indicated. Sites of introns and the sites of subtilisin digestion that releases the carboxy-terminal CRDs of MBPs are underlined. Residues inthe neck–CRD interface (see Table 2) are denoted with asterisks. Sequences and intron positions are derived from [19, 44, 61, 62, 63, 64 and 65]. Figure 8. Representative sequences of the neck region and portions of the CRDs following the last Gly-X-Y repeat taken from various subgroups of collectins. RA, rat; HU, human. The a and d positions of the heptadrepeats are indicated. Sites of introns and the sites of subtilisin digestion that releases the carboxy-terminal CRDs of MBPs are underlined. Residues inthe neck–CRD interface (see [3]Table 2) are denoted with asterisks. Sequences and intron positions are derived from [[4]19, [5]44, [6]61, [7]62, [8]63, [9]64 and [10]65].

The above figures are reproduced from the cited reference with permission from Cell Press

Secondary reference #2

Title

Binding of sugar ligands to ca(2+)-Dependent animal lectins. Ii. Generation of high-Affinity galactose binding by site-Directed mutagenesis.

Authors

S.T.Iobst, K.Drickamer.

Ref.

J Biol Chem, 1994, 269, 15512-15519.

PubMed id

8195195