2ZKN

X-ray structure of mutant galectin-1/lactose complex

Summary for 2ZKN

• Entry DOI: 10.2210/pdb2zkn/pdb
• Related PRD ID: PRD_900004
• Descriptor: Galectin-1, beta-D-galactopyranose-(1-4)-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: beta sandwich, acetylation, lectin, apoptosis
• Biological source: Homo sapiens (Human)
• Cellular location: Secreted, extracellular space, extracellular matrix: P09382
• Total number of polymer chains: 2
• Total formula weight: 29348.47

Authors

Abe, A.,Yoshida, H.,Kamitori, S. (deposition date: 2008-03-26, release date: 2008-09-30, Last modification date: 2023-11-01)

Primary citation

Nishi, N.,Abe, A.,Iwaki, J.,Yoshida, H.,Itoh, A.,Shoji, H.,Kamitori, S.,Hirabayashi, J.,Nakamura, T.
Functional and structural bases of a cysteine-less mutant as a long-lasting substitute for galectin-1
Glycobiology, 18:1065-1073, 2008

PubMed Abstract: Galectin-1 (Gal-1), a member of the beta-galactoside-binding animal lectin family, has a wide range of biological activities, which makes it an attractive target for medical applications. Unlike other galectins, Gal-1 is susceptible to oxidation at cysteine residues, which is troublesome for in vitro/vivo studies. To overcome this problem, we prepared a cysteine-less mutant of Gal-1 (CSGal-1) by substituting all cysteine residues with serine residues. In the case of wild-type Gal-1, the formation of covalent dimers/oligomers was evident after 10 days of storage in the absence of a reducing agent with a concomitant decrease in hemagglutination activity, while CSGal-1 did not form multimers and retained full hemagglutination activity after 400 days of storage. Frontal affinity chromatography showed that the sugar-binding specificity and affinity of Gal-1 for model glycans were barely affected by the mutagenesis. Gal-1 is known to induce cell signaling leading to an increase in the intracytoplasmic calcium concentration and to cell death. CSGal-1 is also capable of inducing calcium flux and growth inhibition in Jurkat cells, which are comparable to or more potent than those induced by Gal-1. The X-ray structure of the CSGal-1/lactose complex has been determined. The structure of CSGal-1 is almost identical to that of wild-type human Gal-1, showing that the amino acid substitutions do not affect the overall structure or carbohydrate-binding site structure of the protein. These results indicate that CSGal-1 can serve as a stable substitute for Gal-1.

PubMed: 18796645
DOI: 10.1093/glycob/cwn089

Experimental method

X-RAY DIFFRACTION (1.86 Å)