3f28

Thermolysin inhibition

spinqualitylabelsall models 3f28, resolution 1.68Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3f28 is a 1 chain structure with sequence from Bacillus thermoproteolyticus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CA, S7B, ZN Related: 8tln, 1tmn, 3f2p Activity: Thermolysin, with EC number 3.4.24.27 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [THER_BACTH] Extracellular zinc metalloprotease. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Fragment-based drug discovery has gained a foothold in today's lead identification processes. We present the application of in silico fragment-based screening for the discovery of novel lead compounds for the metalloendoproteinase thermolysin. We have chosen thermolysin to validate our screening approach as it is a well-studied enzyme and serves as a model system for other proteases. A protein-targeted virtual library was designed and screening was carried out using the program AutoDock. Two fragment hits could be identified. For one of them, the crystal structure in complex with thermolysin is presented. This compound was selected for structure-based optimization of binding affinity and improvement of ligand efficiency, while concomitantly keeping the fragment-like properties of the initial hit. Redesigning the zinc coordination group revealed a novel class of fragments possessing K(i) values as low as 128 muM, thus they provide a good starting point for further hit evolution in a tailored lead design. Fragment-Based Lead Discovery: Screening and Optimizing Fragments for Thermolysin Inhibition.,Englert L, Silber K, Steuber H, Brass S, Over B, Gerber HD, Heine A, Diederich WE, Klebe G ChemMedChem. 2010 Apr 14. PMID:20394106 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Thermolysin

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