1HKK
High resoultion crystal structure of human chitinase in complex with allosamidin
Summary for 1HKK
| Entry DOI | 10.2210/pdb1hkk/pdb |
| Related | 1GUV 1HKI 1HKJ 1HKM 1LG1 1LG2 1LQ0 1WAW 1WB0 |
| Descriptor | CHITOTRIOSIDASE-1, 2-acetamido-2-deoxy-beta-D-allopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-allopyranose, ALLOSAMIZOLINE, ... (5 entities in total) |
| Functional Keywords | human chitinase, hydrolase, chitin degradation, allosamidin |
| Biological source | HOMO SAPIENS (HUMAN) |
| Total number of polymer chains | 1 |
| Total formula weight | 42174.13 |
| Authors | Rao, F.V.,Houston, D.R.,Boot, R.G.,Aerts, J.M.F.G.,Sakuda, S.,Van Aalten, D.M.F. (deposition date: 2003-03-10, release date: 2004-03-11, Last modification date: 2024-11-06) |
| Primary citation | Rao, F.V.,Houston, D.R.,Boot, R.G.,Aerts, J.M.F.G.,Sakuda, S.,Van Aalten, D.M.F. Crystal Structures of Allosamidin Derivatives in Complex with Human Macrophage Chitinase. J.Biol.Chem., 278:20110-, 2003 Cited by PubMed Abstract: The pseudotrisaccharide allosamidin is a potent family 18 chitinase inhibitor with demonstrated biological activity against insects, fungi, and the Plasmodium falciparum life cycle. The synthesis and biological properties of several derivatives have been reported. The structural interactions of allosamidin with several family 18 chitinases have been determined by x-ray crystallography previously. Here, a high resolution structure of chitotriosidase, the human macrophage chitinase, in complex with allosamidin is presented. In addition, complexes of the allosamidin derivatives demethylallosamidin, methylallosamidin, and glucoallosamidin B are described, together with their inhibitory properties. Similar to other chitinases, inhibition of the human chitinase by allosamidin derivatives lacking a methyl group is 10-fold stronger, and smaller effects are observed for the methyl and C3 epimer derivatives. The structures explain the effects on inhibition in terms of altered hydrogen bonding and hydrophobic interactions, together with displaced water molecules. The data reported here represent a first step toward structure-based design of specific allosamidin derivatives. PubMed: 12639956DOI: 10.1074/JBC.M300362200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.85 Å) |
Structure validation
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