PDBsum entry 1w6m

Sugar binding protein

PDB id: 1w6m

Contents

Protein chain

134 a.a. *

Ligands

BME ×5

SO4 ×2

GAL ×2

Waters ×131

* Residue conservation analysis

PDB id:

1w6m

Name:

Sugar binding protein

Title:

X-ray crystal structure of c2s human galectin-1 complexed with galactose

Structure:

Galectin-1. Chain: a. Synonym: beta-galactoside-binding lectin l-14-i, hpl, lactose-binding lectin 1, s-lac lectin 1, galaptin, hbl. Engineered: yes. Mutation: yes. Galectin-1. Chain: b. Synonym: beta-galactoside-binding lectin l-14-i, lactose-binding

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PDB file)

Resolution:

2.30Å R-factor: 0.201 R-free: 0.241

Authors:

M.I.F.Lopez-Lucendo,H.J.Gabius,A.Romero

Key ref:

M.F.López-Lucendo et al. (2004). Growth-regulatory human galectin-1: crystallographic characterisation of the structural changes induced by single-site mutations and their impact on the thermodynamics of ligand binding. J Mol Biol, 343, 957-970. PubMed id: 15476813 DOI: 10.1016/j.jmb.2004.08.078

Date:

19-Aug-04 Release date: 20-Oct-04

Protein chains

P09382  (LEG1_HUMAN) -  Galectin-1 from Homo sapiens

Seq: 135 a.a.

Struc: 134 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

DOI no: 10.1016/j.jmb.2004.08.078

J Mol Biol 343:957-970 (2004)

PubMed id: 15476813

Growth-regulatory human galectin-1: crystallographic characterisation of the structural changes induced by single-site mutations and their impact on the thermodynamics of ligand binding.

M.F.López-Lucendo, D.Solís, S.André, J.Hirabayashi, K.Kasai, H.Kaltner, H.J.Gabius, A.Romero.

ABSTRACT

Human galectin-1 is a potent multifunctional effector that participates in specific protein-carbohydrate and protein-protein (lipid) interactions. By determining its X-ray structure, we provide the basis to define the structure of its ligand-binding pocket and to perform rational drug design. We have also analysed whether single-site mutations introduced at some distance from the carbohydrate recognition domain can affect the lectin fold and influence sugar binding. Both the substitutions introduced in the C2S and R111H mutants altered the presentation of the loop, harbouring Asp123 in the common "jelly-roll" fold. The orientation of the side-chain was inverted 180 degrees and the positions of two key residues in the sugar-binding site of the R111H mutant were notably shifted, i.e. His52 and Trp68. Titration calorimetry was used to define the decrease in ligand affinity in both mutants and a significant increase in the entropic penalty was found to outweigh a slight enhancement of the enthalpic contribution. The position of the SH-groups in the galectin appeared to considerably restrict the potential to form intramolecular disulphide bridges and was assumed to be the reason for the unstable lectin activity in the absence of reducing agent. However, this offers no obvious explanation for the improved stability of the C2S mutant under oxidative conditions. The noted long-range effects in single-site mutants are relevant for the functional divergence of closely related galectins and in more general terms, the functionality definition of distinct amino acids.

Selected figure(s)

Figure 2.
Figure 2. Ribbon diagram of the homodimeric human galectin-1 prepared with MOLSCRIPT.70 The b-strands in the five-stranded (F1-F5) and six-stranded (S1-S6a/S6b) b-sheets are indicated by the letter-number code.

Figure 5.
Figure 5. The carbohydrate recognition site of hGal-1. (a) The binding site in free hGal-1, showing the position of bound water molecules as green spheres. The three water molecules are placed at the sites of interaction with the hydroxyl groups O4, O6 of galactose and O3 of glucose, when the ligand enters the binding site. (b) A view of the CRD of wt hGal-1 complexed with lactose. The carbohydrate-binding cleft is discernible in the concave face of the S4-S6a/S6b b-sheet. The lactose moiety and the side-chains of the sugar-binding residues are shown as stick-and-ball models.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2004, 343, 957-970) copyright 2004.

Figures were selected by the author.