Mistletoe lectin I in complex with galactose and lactose reveals distinct sugar-binding properties
- Institute of Biochemistry and Food Chemistry, University of Hamburg, c/o DESY, Notkestrasse 85, Building 22a, 22603 Hamburg (Germany)
- Institute of Physiological Chemistry, University of Tübingen, Hoppe-Seyler-Strasse 4, 72076 Tübingen (Germany)
- Department of Physics, IBILCE/UNESP, São Jose do Rio Preto, São Paul (Brazil)
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi (India)
- Institute of Crystallography of Russian Academy of Sciences, Leninsky Prospect 59, 117333 Moscow (Russian Federation)
The structures of mistletoe lectin I in complex with lactose and galactose reveal differences in binding by the two known sites in subdomains α1 and γ2 and suggest the presence of a third low-affinity site in subdomain β1. The structures of mistletoe lectin I (ML-I) from Viscum album complexed with lactose and galactose have been determined at 2.3 Å resolution and refined to R factors of 20.9% (R{sub free} = 23.6%) and 20.9 (R{sub free} = 24.6%), respectively. ML-I is a heterodimer and belongs to the class of ribosome-inactivating proteins of type II, which consist of two chains. The A-chain has rRNA N-glycosidase activity and irreversibly inhibits eukaryotic ribosomes. The B-chain is a lectin and preferentially binds to galactose-terminated glycolipids and glycoproteins on cell membranes. Saccharide binding is performed by two binding sites in subdomains α1 and γ2 of the ML-I B-chain separated by ∼62 Å from each other. The favoured binding of galactose in subdomain α1 is achieved via hydrogen bonds connecting the 4-hydroxyl and 3-hydroxyl groups of the sugar moiety with the side chains of Asp23B, Gln36B and Lys41B and the main chain of 26B. The aromatic ring of Trp38B on top of the preferred binding pocket supports van der Waals packing of the apolar face of galactose and stabilizes the sugar–lectin complex. In the galactose-binding site II of subdomain γ2, Tyr249B provides the hydrophobic stacking and the side chains of Asp235B, Gln238B and Asn256B are hydrogen-bonding partners for galactose. In the case of the galactose-binding site I, the 2-hydroxyl group also stabilizes the sugar–protein complex, an interaction thus far rarely detected in galactose-specific lectins. Finally, a potential third low-affinity galactose-binding site in subunit β1 was identified in the present ML-I structures, in which a glycerol molecule from the cryoprotectant buffer has bound, mimicking the sugar compound.
- OSTI ID:
- 22356100
- Journal Information:
- Acta Crystallographica. Section F, Vol. 61, Issue Pt 1; Other Information: PMCID: PMC1952410; PMID: 16508080; PUBLISHER-ID: en5086; OAI: oai:pubmedcentral.nih.gov:1952410; Copyright (c) International Union of Crystallography 2005; Country of input: International Atomic Energy Agency (IAEA); ISSN 1744-3091
- Country of Publication:
- United Kingdom
- Language:
- English
Similar Records
Quantitation of two endogenous lactose-inhibitable lectins in embryonic and adult chicken tissues
Stability and Sugar Recognition Ability of Ricin-Like Carbohydrate Binding Domains