1LQ0
CRYSTAL STRUCTURE OF HUMAN CHITOTRIOSIDASE AT 2.2 ANGSTROM RESOLUTION
Summary for 1LQ0
| Entry DOI | 10.2210/pdb1lq0/pdb |
| Related | 1LG1 1LG2 |
| Descriptor | CHITOTRIOSIDASE (2 entities in total) |
| Functional Keywords | chitinase, chitin, gaucher, hydrolase |
| Biological source | Homo sapiens (human) |
| Cellular location | Secreted: Q13231 |
| Total number of polymer chains | 1 |
| Total formula weight | 40784.69 |
| Authors | Fusetti, F.,Rozeboom, H.J.,Dijkstra, B.W. (deposition date: 2002-05-08, release date: 2003-07-29, Last modification date: 2024-10-30) |
| Primary citation | Fusetti, F.,Von Moeller, H.,Houston, D.,Rozeboom, H.J.,Dijkstra, B.W.,Boot, R.G.,Aerts, J.M.,Van Aalten, D.M. Structure of human chitotriosidase. Implications for specific inhibitor design and function of mammalian chitinase-like lectins J.Biol.Chem., 277:25537-25544, 2002 Cited by PubMed Abstract: Chitin hydrolases have been identified in a variety of organisms ranging from bacteria to eukaryotes. They have been proposed to be possible targets for the design of novel chemotherapeutics against human pathogens such as fungi and protozoan parasites as mammals were not thought to possess chitin-processing enzymes. Recently, a human chitotriosidase was described as a marker for Gaucher disease with plasma levels of the enzyme elevated up to 2 orders of magnitude. The chitotriosidase was shown to be active against colloidal chitin and is inhibited by the family 18 chitinase inhibitor allosamidin. Here, the crystal structure of the human chitotriosidase and complexes with a chitooligosaccharide and allosamidin are described. The structures reveal an elongated active site cleft, compatible with the binding of long chitin polymers, and explain the inactivation of the enzyme through an inherited genetic deficiency. Comparison with YM1 and HCgp-39 shows how the chitinase has evolved into these mammalian lectins by the mutation of key residues in the active site, tuning the substrate binding specificity. The soaking experiments with allosamidin and chitooligosaccharides give insight into ligand binding properties and allow the evaluation of differential binding and design of species-selective chitinase inhibitors. PubMed: 11960986DOI: 10.1074/jbc.M201636200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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