5aen
From Proteopedia
Structure of human Leukotriene A4 hydrolase in complex with inhibitor dimethyl(2- (4-phenoxyphenoxy)ethyl)amine
Structural highlights
Function[LKHA4_HUMAN] Epoxide hydrolase that catalyzes the final step in the biosynthesis of the proinflammatory mediator leukotriene B4. Has also aminopeptidase activity.[1] [2] [3] [4] [5] [6] [7] Publication Abstract from PubMedThe 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. PENG: A Neural Gas-Based Approach for Pharmacophore Elucidation. Method Design, Validation, and Virtual Screening for Novel Ligands of LTA4H.,Moser D, Wittmann SK, Kramer J, Blocher R, Achenbach J, Pogoryelov D, Proschak E J Chem Inf Model. 2015 Feb 9. PMID:25625859[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
Categories: Achenbach, J | Blocher, R | Kramer, J | Moser, D | Pogoryelov, D | Proschak, E | Wittmann, S K | Hydrolase | Lta4h
