4R9A

Crystal structure of Human galectin-3 CRD in complex with lactose (pH 7.0, PEG4000)

Summary for 4R9A

• Entry DOI: 10.2210/pdb4r9a/pdb
• Related: 4R9B 4R9C 4R9D 4RL7
• Related PRD ID: PRD_900004
• Descriptor: Galectin-3, beta-D-galactopyranose-(1-4)-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: sugar binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 16584.95

Authors

Su, J.Y. (deposition date: 2014-09-04, release date: 2015-03-11, Last modification date: 2024-05-29)

Primary citation

Su, J.,Zhang, T.,Wang, P.,Liu, F.,Tai, G.,Zhou, Y.
The water network in galectin-3 ligand binding site guides inhibitor design.
Acta Biochim.Biophys.Sin., 47:192-198, 2015

PubMed Abstract: Galectin-3 (Gal-3) which shows affinity of β-galactosides is a cancer-related protein. Thus, it is important to understand its ligand binding mechanism and then design its specific inhibitor. It was suggested that the positions of water molecules in Gal-3 ligand-binding site could be replaced by appropriate chemical groups of ideal inhibitors. However, the reported structures of Gal-3 carbohydrate recognition domain (CRD) complexed with lactose showed that the number of water molecules are different and the water positions are inconsistent in the ligand-binding site. This study reported four high-resolution (1.24-1.19 Å) structures of Gal-3 CRD complexed with lactose, and accurately located 12 conserved water molecules in the water network of Gal-3 CRD ligand-binding site by merging these structures. These water molecules either directly stabilize the binding of Gal-3 CRD and lactose, or hold the former water molecules at the right place. In particular, water molecule 4 (W4) which only coordinates with water molecule 5 (W5) and water molecule 6 (W6) plays a key role in stabilizing galactose residue. In addition, by three-dimensional alignment of the positions of all residues, 14 flexible parts of Gal-3 CRD were found to dynamically fluctuate in the crystalline environment.

PubMed: 25662390
DOI: 10.1093/abbs/gmu132

Experimental method

X-RAY DIFFRACTION (1.197 Å)