Family 18 chitolectins: comparison of MGP40 and HUMGP39

Abstract

Glycosidase and lectins both bind sugars, but only the glycosidases have catalytic activity. The glycosidases occur among over 100 evolved protein families and Family 18 is one of the two chitinases (EC 3, 2.1.14) families. Interestingly, lectins are also in this evolutionary group of Family 18 glycosidase proteins. The proteins belonging to the enzymatically inactive class are referred to as chitolectins and have a binding site that is highly similar to the catalytic Family 18 enzymes. We present a comparison of the recently obtained structures of two Family 18 chitolectins, MGP40 [A.K. Mohanty, G. Singh, M. Paramasivam, K. Saravanan, T. Jabeen, S. Sharma, S. Yadav, P. Kaur, P. Kumar, A. Srinivasan, T.P. Singh, Crystal structure of a novel regulatory 40kDa mammary gland protein (MGP-40) secreted during involution, J. Biol. Chem. 278 (2003) 14451-14460.] and HumGP39 [F. Fusetti, T. Pijning, K.H. Kalk, E. Bos, B.W. Dijkstra, Crystal structure and carbohydrate-binding properties of the human cartilage glycoprotein-39, J. Biol. Chem. 278 (2003) 37753-37760; D.R. Houston, D.R. Anneliese, C.K. Joanne, D.M.V. Aalten, Structure and ligand-induced conformational change of the 39kDa glycoprotein from human articular chondrocytes, J. Biol. Chem. 278 (2003) 30206-30212.] with a focus on the glycosidase active site. We compare the sequence and the structure of these two Family 18 protein classes. The difference between the active and inactive protein is a glutamic acid which acts as the essential acid/base residue for chitin cleavage and is replaced with leucine or glutamine in the chitolectins. Furthermore, a mechanism for the interaction between the chitolectin and oligosaccharides was proposed.

Fig. 1

Sequence alignment for Human GP39 (362 residues); Goat MGP40 (362 residues); and Human Chitotriosidase (366 residues) is shown. Identity (*), 181 residues, 49.05%; strongly similar (:), 78 residues, 21.14%; Weakly similar (.), 41 residues, 11.11%; Different 69 residues, 18.70%.

Fig 2

Residues within 4.5 Å of the sugar residues in the hexasaccharide-bound HumGP39 structure

Fig. 3

Backbone of the residues 74–86 of MGP40 (red) and equivalent residues 95–107 of HumGP39 (green) are shown. Sidechains of Trp 78 (MGP40) and Trp 99 (HumGP39) are also shown. The −1 +1 sugars found in the HumGP39 structure are shown in blue. The proteins and sugar are depicted in stick configuration.

Fig. 4

Trp99 of HumGP39 protein along with the binding sugars is shown in stick configuration. Trp99 of HumGP39 from a structure with no sugar bound (PDB code: 1HJX) is shown in red and with sugar bound (PDB code: 1HJW) is shown in green. The bound sugars at −1 and +1 positions are shown in blue. The proteins and sugar are shown in stick configuration