Active Site Mapping of an Aspartic Protease by Multiple Fragment Crystal Structures: Versatile Warheads To Address a Catalytic Dyad
Radeva N, Schiebel J, Wang X, Krimmer S, Fu K, Stieler M, Ehrmann F, Metz A, Rickmeyer T, Betz M, Winquist J, Park A, Huschmann F, Weiss M, Mueller U, Heine A, Klebe G. Active Site Mapping of an Aspartic Protease by Multiple Fragment Crystal Structures: Versatile Warheads To Address a Catalytic Dyad. Journal Of Medicinal Chemistry 2016, 59: 9743-9759. PMID: 27726357, DOI: 10.1021/acs.jmedchem.6b01195.Peer-Reviewed Original ResearchConceptsFunctional groupsAspartic protease endothiapepsinCatalytic dyadCarboxylic acid fragmentOxygen functional groupsNovel functional groupsActive site mappingSteric demandWater moleculesFragment-growing strategyCrystal structureSide chainsFragment libraryHigh-quality crystalsS1 pocketScreening cascadeAcid fragmentCrystallographySpecificity pocketRelated fragmentsWarhead