1HKM

High resolution crystal structure of human chitinase in complex with demethylallosamidin

1HKM の概要

• エントリーDOI: 10.2210/pdb1hkm/pdb
• 関連するPDBエントリー: 1GUV 1HKI 1HKJ 1HKK 1LG1 1LG2
• 分子名称: CHITOTRIOSIDASE, 2-acetamido-2-deoxy-beta-D-allopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-allopyranose, METHYL N-ACETYL ALLOSAMINE, ... (4 entities in total)
• 機能のキーワード: human chitinase, hydrolase, chitin degradation, demethylallosamidin
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 41408.30

構造登録者

Rao, F.V.,Houston, D.R.,Boot, R.G.,Aerts, J.M.F.G.,Sakuda, S.,Van Aalten, D.M.F. (登録日: 2003-03-10, 公開日: 2004-03-11, 最終更新日: 2024-11-13)

主引用文献

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

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: 12639956
DOI: 10.1074/JBC.M300362200

実験手法

X-RAY DIFFRACTION (2.55 Å)