Biomedical Engineering Reference
In-Depth Information
C-CRD but as no x-ray crystallography is available for this CRD the hydrogen bridges have
not been verified yet. Additional residues are involved in the conserved binding process
either by hydrogen bonding (Glu184, Asn174, numbering according to human galectin-3,
see Fig. 3) or van-der-Waals interaction (Trp181, numbering according to human galectin-3)
(Di Lella et al., 2009; Diehl et al., 2010; Lobsanov et al., 1993; Seetharaman et al., 1998).
Fig. 3
.
Human galectin-3 with bound galactose unit of LacNAc
PDB 1KJL
. H-bondings are
shown as dotted lines for residues H158 (C4-OH), N160 (C4-OH), R162 (C4-OH and
intramolecular O-atom), N174 (C6-OH), E184 (C6-OH) (Seetharaman et al., 1998; Sörme et
al., 2005). Picture made with SwissProt pdb viewer (Guex & Peitsch, 1997).
The importance of the mentioned H-bonding amino acids has been proven by site-directed
mutagenesis performed with human galectin-1. In those experiments the change of single
amino acids involved in H-bonding eliminates the binding to lactose-sepharose and/or
asialofetuin (Hirabayashi & Kasai, 1991; Hirabayashi & Kasai, 1994). Although binding is
not completely abolished, significant influence of the conserved Trp residue for sugar
binding was also proven in bovine and human galectin-1 (Abbott & Feizi, 1991; Hirabayashi
& Kasai, 1991).
Arg186 is not completely conserved throughout the different galectins (see Fig. 2, elipse).
The N-terminal domain of galectin-8 for example presents an Ile at the corresponding
position resulting in a differing fine specificity for glycans. Due to this mutation galectin-8
N-CRD favours lactose structures over LacNAc type II structures in the binding site.
Thereby different biological functions of galectin-8 in contrast to other galectins such
as galectin-3 are regulated (Salomonsson et al., 2010). Specific binding preferences resulting
from the differences in amino acid sequence will be discussed in chapter 4 in more detail.
