2EAK

Crystal structure of human galectin-9 N-terminal CRD in complex with lactose

Summary for 2EAK

• Entry DOI: 10.2210/pdb2eak/pdb
• Related: 2EAG 2EAH 2EAI 2EAJ 2EAL
• Related PRD ID: PRD_900008
• Descriptor: Galectin-9, beta-D-galactopyranose-(1-4)-alpha-D-glucopyranose, (2S,3S)-1,4-DIMERCAPTOBUTANE-2,3-DIOL, ... (5 entities in total)
• Functional Keywords: beta sandwich, carbohydrate binding protein, galectin, sugar binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 3
• Total formula weight: 50006.00

Authors

Nagae, M.,Nakamura-Tsuruta, S.,Nishi, N.,Nakamura, T.,Hirabayashi, J.,Wakatsuki, S.,Kato, R. (deposition date: 2007-01-31, release date: 2007-09-25, Last modification date: 2024-12-25)

Primary citation

Nagae, M.,Nishi, N.,Nakamura-Tsuruta, S.,Hirabayashi, J.,Wakatsuki, S.,Kato, R.
Structural analysis of the human galectin-9 N-terminal carbohydrate recognition domain reveals unexpected properties that differ from the mouse orthologue.
J.Mol.Biol., 375:119-135, 2008

PubMed Abstract: Galectins are a family of beta-galactoside-binding lectins that contain a conserved carbohydrate recognition domain (CRD). They exhibit high affinities for small beta-galactosides as well as variable binding specificities for complex glycoconjugates. Structural and biochemical analyses of the mechanism governing specific carbohydrate recognition provide a useful template to elucidate the function of these proteins. Here we report the crystal structures of the human galectin-9 N-terminal CRD (NCRD) in the presence of lactose and Forssman pentasaccharide. Mouse galectin-9 NCRD, the structure of which was previously solved by our group, forms a non-canonical dimer in both the crystal state and in solution. Human galectin-9 NCRD, however, exists as a monomer in crystals, despite a high sequence identity to the mouse homologue. Comparative frontal affinity chromatography analysis of the mouse and human galectin-9 NCRDs revealed different carbohydrate binding specificities, with disparate affinities for complex glycoconjugates. Human galectin-9 NCRD exhibited a high affinity for Forssman pentasaccharide; the association constant for mouse galectin-9 NCRD was 100-fold less than that observed for the human protein. The combination of structural data with mutational studies demonstrated that non-conserved amino acid residues on the concave surface were important for determination of target specificities. The human galectin-9 NCRD exhibited greater inhibition of cell proliferation than the mouse NCRD. We discuss the biochemical and structural differences between highly homologous proteins from different species.

PubMed: 18005988
DOI: 10.1016/j.jmb.2007.09.060

Experimental method

X-RAY DIFFRACTION (1.97 Å)