5AEN

Structure of human Leukotriene A4 hydrolase in complex with inhibitor dimethyl(2- (4-phenoxyphenoxy)ethyl)amine

5AEN の概要

• エントリーDOI: 10.2210/pdb5aen/pdb
• 分子名称: LEUKOTRIENE A-4 HYDROLASE, N,N-dimethyl-2-(4-phenoxyphenoxy)ethanamine, ZINC ION, ... (6 entities in total)
• 機能のキーワード: hydrolase, leukotriene (lt) a4 hydrolase/aminopeptidase, lta4h
• 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: 70159.61

構造登録者

Moser, D.,Wittmann, S.K.,Kramer, J.,Blocher, R.,Achenbach, J.,Pogoryelov, D.,Proschak, E. (登録日: 2015-01-06, 公開日: 2015-02-11, 最終更新日: 2024-01-10)

主引用文献

Moser, D.,Wittmann, S.K.,Kramer, J.,Blocher, R.,Achenbach, J.,Pogoryelov, D.,Proschak, E.
Peng: A Neural Gas-Based Approach for Pharmacophore Elucidation. Method Design, Validation and Virtual Screening for Novel Ligands of Lta4H.
J.Chem.Inf.Model., 55:284-, 2015

PubMed Abstract: The pharmacophore concept is commonly employed in virtual screening for hit identification. A pharmacophore is generally defined as the three-dimensional arrangement of the structural and physicochemical features of a compound responsible for its affinity to a pharmacological target. Given a number of active ligands binding to a particular target in the same manner, it can reasonably be assumed that they have some shared features, a common pharmacophore. We present a growing neural gas (GNG)-based approach for the extraction of the relevant features which we called PENG (pharmacophore elucidation by neural gas). Results of retrospective validation indicate an acceptable quality of the generated models. Additionally a prospective virtual screening for leukotriene A4 hydrolase (LTA4H) inhibitors was performed. LTA4H is a bifunctional zinc metalloprotease which displays both epoxide hydrolase and aminopeptidase activity. We could show that the PENG approach is able to predict the binding mode of the ligand by X-ray crystallography. Furthermore, we identified a novel chemotype of LTA4H inhibitors.

PubMed: 25625859
DOI: 10.1021/CI500618U

実験手法

X-RAY DIFFRACTION (1.864 Å)