5GM0

Tl-gal with lactose

Summary for 5GM0

• Entry DOI: 10.2210/pdb5gm0/pdb
• Related: 5GLT 5GLU 5GLV 5GLW 5GLZ
• Related PRD ID: PRD_900004
• Descriptor: galectin, beta-D-galactopyranose-(1-4)-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: carbohydrates, toxascaris leonina, galectin, sugar binding protein
• Biological source: Toxascaris leonina
• Total number of polymer chains: 2
• Total formula weight: 65675.23

Authors

Hwang, E.Y. (deposition date: 2016-07-12, release date: 2016-11-09, Last modification date: 2023-11-08)

Primary citation

Hwang, E.Y.,Jeong, M.S.,Park, S.K.,Ha, S.C.,Yu, H.S.,Jang, S.B.
Structural Basis for Carbohydrate Recognition and Anti-inflammatory Modulation by Gastrointestinal Nematode Parasite Toxascaris leonina Galectin
J. Biol. Chem., 291:25326-25338, 2016

PubMed Abstract: Toxascaris leonina galectin (Tl-gal) is a galectin-9 homologue protein isolated from an adult worm of the canine gastrointestinal nematode parasite, and Tl-gal-vaccinated challenge can inhibit inflammation in inflammatory bowel disease-induced mice. We determined the first X-ray structures of full-length Tl-gal complexes with carbohydrates (lactose, N-acetyllactosamine, lacto-N-tetraose, sialyllactose, and glucose). Bonds were formed on concave surfaces of both carbohydrate recognition domains (CRDs) in Tl-gal. All binding sites were found in the HXXXR and WGXEER motifs. Charged Arg/Arg and Glu/Glu on the conserved motif of Tl-gal N-terminal CRD and C-terminal CRD are critical amino acids for recognizing carbohydrate binding, and the residues can affect protein folding and structure. The polar amino acids His, Asn, and Trp are also important residues for the interaction with carbohydrates through hydrogen bonding. Hemagglutination activities of Tl-gal were inhibited by interactions with carbohydrates and mutations. We found that the mutation of Tl-gal (E80A/E215A) at the carbohydrate binding region induced protein aggregation and could be caused in many diseases. The short linker region between the N-terminal and C-terminal CRDs of Tl-gal was very stable against proteolysis and maintained its biological activity. This structural information is expected to elucidate the carbohydrate recognition mechanism of Tl-gal and improve our understanding of anti-inflammatory mediators and modulators of immune response.

PubMed: 27742836
DOI: 10.1074/jbc.M116.743773

Experimental method

X-RAY DIFFRACTION (1.7 Å)