6tx4

CRYSTAL STRUCTURE OF HUMAN FKBP51 FK1 DOMAIN A19T MUTANT IN COMPLEX WITH 2-PYRIDONE

spinqualitylabelsall models 6tx4, resolution 1.06Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6tx4 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.06Å Ligands: CL, HRZ, NA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function FKBP5_HUMAN Interacts with functionally mature heterooligomeric progesterone receptor complexes along with HSP90 and TEBP. Publication Abstract from PubMed Fragment-based drug discovery (FBDD) deploys efficient sampling of the vast chemical space for hit identification. Libraries are screened biophysically and fragment:protein co-structures are determined by X-ray crystallography. In parallel, computational methods can derive pharmacophore models or screen virtual libraries. We screened 15 very small fragments (VSFs) (HA <= 11) computationally, using site-identification by ligand competitive saturation (SILCS), and experimentally, by X-ray crystallography, to map potential interaction sites on the FKBP51 FK1 domain. We identified three hot spots and obtained 6 X-ray co-structures, giving a hit rate of 40%. SILCS FragMaps overlapped with X-ray structures. The compounds had millimolar affinities as determined by (15)N HSQC NMR. VSFs identified the same interactions as known FK1 binder and provide new chemical starting points. We propose a hybrid screening strategy starting with SILCS, followed by a pharmacophore-derived X-ray screen and (15)N HSQC NMR based KD determination to rapidly identify hits and their binding poses. A hybrid screening approach for very small fragments - X-ray and Computational Screening on FKBP51.,Draxler SW, Bauer M, Eickmeier C, Nadal S, Nar H, Rangel D, Seeliger D, Zeeb M, Fiegen D J Med Chem. 2020 May 18. doi: 10.1021/acs.jmedchem.0c00120. PMID:32420743 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also FKBP 3D structures

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