PDBsum entry 3ikn

Sugar binding protein

PDB id: 3ikn

Contents

Protein chain

152 a.a.

Ligands

GAL ×3

Metals

_CA ×10

Waters ×492

References listed in PDB file

Key reference

Title

Structural characterisation of ligand-Binding determinants in human lung surfactant protein d: influence of asp325.

Authors

A.K.Shrive, C.Martin, I.Burns, J.M.Paterson, J.D.Martin, J.P.Townsend, P.Waters, H.W.Clark, U.Kishore, K.B.Reid, T.J.Greenhough.

Ref.

J Mol Biol, 2009, 394, 776-788. [DOI no: 10.1016/j.jmb.2009.09.057]

PubMed id

19799916

Abstract

The crystal structures of a biologically and therapeutically active recombinant homotrimeric fragment of human lung surfactant protein D with a series of bound ligands have been determined. While the structures reveal various different binding modes, all utilise a similarly positioned pair of mannose-type O3' and O4' hydroxyls with no direct interaction between any non-terminal sugar and protein. The orientation, position, and interactions of the bound terminal sugar depend on the sugar itself, the presence and form of glycosidic linkage, and the environment in the crystal, which, via Asp325, places stereochemical and electronic constraints, different for the three different subunits in the homotrimer, on the ligand-binding site. As a direct consequence of this influence, the other binding-pocket flanking residue, Arg343, exhibits variable conformation and variable interactions with bound ligand and leaves open to question which orientation of terminal mannobiose, and of other terminal disaccharides, may be present in extended physiological ligands. The combined structural evidence shows that there is significant flexibility in recognition; that Asp325, in addition to Arg343, is an important determinant of ligand selectivity, recognition, and binding; and that differences in crystal contact interfaces exert, through Asp325, significant influence on preferred binding modes.

Figure 2.
Fig. 2. The manα1–2man-bound rfhSP-D trimer showing the bound manα1–2man (only the terminal mannose man1 is visible in the electron density) and the calcium ions (green spheres). (a) Viewed down the molecular 3-fold axis. (b) Viewed perpendicular to the molecular 3-fold axis.

Figure 3.
Fig. 3. The coordination of the calcium ion Ca1 and the bound ligands in selected subunits of the rfhSP-D–ligand complexes. (a) Chain B of the inositol phosphate structure. (b) Chain A, maltose. (c) Chain A, galactose. (d) Chain A, manα1–2man. (e) Chain B, manα1–4man. (f) Chain A, manα1–4man.

The above figures are reprinted from an Open Access publication published by Elsevier: J Mol Biol (2009, 394, 776-788) copyright 2009.

Secondary reference #1

Title

High-Resolution structural insights into ligand binding and immune cell recognition by human lung surfactant protein d.

Authors

A.K.Shrive, H.A.Tharia, P.Strong, U.Kishore, I.Burns, P.J.Rizkallah, K.B.Reid, T.J.Greenhough.

Ref.

J Mol Biol, 2003, 331, 509-523. [DOI no: 10.1016/S0022-2836(03)00761-7]

PubMed id

12888356

Figure 3.
Figure 3. The maltose-bound rfhSP-D trimer showing the bound maltose, the three calcium ions and the central asymmetric tyrosine C228 (generated using MOLSCRIPT.[39.]) (a) Viewed down the molecular 3-fold; (b) viewed perpendicular to the molecular 3-fold.

Figure 7.
Figure 7. Stereoviews (maltose-bound structure) of the neck-CRD interface and interactions. Chain A is in yellow, B in blue and C in red. (a) The interface between CRD A and neck C showing the asymmetric residues TyrC228 and LysA229. The LysC230-GlyA265 contact is present due only to a crystal contact (see the text). (b) The interface between CRD B and neck A showing the asymmetric GluB232 (maltose-bound structure only). The conformation of His220 differs from that in (a) due to a crystal contact. Figure generated using MOLSCRIPT.[39.]

The above figures are reproduced from the cited reference with permission from Elsevier