¡¡
¡¡
¡¡
Abstract
¡¡
Vol 47 No. 3: 192-198 [PDF] [Full Text]
¡¡
The water network in galectin-3 ligand binding site guides inhibitor design
¡¡
Jiyong Su, Tao Zhang, Peiqi Wang, Fengjian Liu, Guihua Tai and Yifa Zhou*
¡¡
School of Life Sciences, Northeast Normal University, Changchun 130024, China
¡¡

Abstract  Galectin-3 (Gal-3) which shows affinity of ¦Â-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¨C1.19 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.

¡¡

Keywords   co-crystal structure; galectin-3; lactose; water molecule; drug design

¡¡

Received   2014-9-20¡¡¡¡
Accepted  
2014-12-26

¡¡

Funding  Galectin-3 (Gal-3) which shows affinity of ¦Â-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

¡¡

* Correspondence address  Tel/Fax: +86-431-85098212; E-mail: [email protected]

¡¡
Browse:183
¡¡
Manuscript Submission

    ScholarOne Manuscripts

User ID

Password

           

    Password Help

E-Mail

¡¡
¡¡
Copyright 1999-2015    Acta Biochimica et Biophysica Sinica    All Rights Reserved
Address: Room 407, Building 31B, 319 Yueyang Road, Shanghai, 200031 P.R. China
Fax: 86-21-54920954    Email: [email protected]
¡¡
»¦ICP±¸05033115ºÅ  |   ÄúÊÇµÚ Î»·ÃÎÊÕߣ¬»¶Ó­£¡