Homology modeling of 3D structure of human chitinase-like protein CHI3L2

Abstract

The human genome encodes six proteins of family 18 glycosyl hydrolases, two active chitinases and four chitinase-like lectins (chi-lectins) lacking catalytic activity. The present article is dedicated to homology modeling of 3D structure of human chitinase 3-like 2 protein (CHI3L2), which is overexpressed in glial brain tumors, and its structural comparison with homologous chi-lectin CHI3L1. Two crystal structures of CHI3L1 in free state (Protein Data Bank codes 1HJX and 1NWR) were used as structural templates for the homology modeling by Modeller 9. 7 program, and the best quality model structure was selected from the obtained model ensemble. Analysis of potential oligosaccharide-binding groove structures of CHI3L1 and CHI3L2 revealed significant differences between these two homologous proteins. 8 of 19 amino acid residues important for ligand binding are substituted in CHI3L2: Tyr34/Asp39, Trp69/Lys74, Trp71/Lys76, Trp99/Tyr104, Asn100/Leu105, Met204/Leu210, Tyr206/Phe212 and Arg263/His271. The differences between these residues could influence the structure of the ligand-binding groove and substantially change the ability of CHI3L2 to bind oligosaccharide ligands. © 2010 Versita Warsaw and Springer-Verlag Wien.