5mb0

Cocktail experiment A: fragments 63, 267, and 291 in complex with Endothiapepsin

spinqualitylabelsall models 5mb0, resolution 1.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5mb0 is a 1 chain structure with sequence from Cryphonectria parasitica. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 47V, DMS, F63, F91, GOL Related: 3t7p Activity: Endothiapepsin, with EC number 3.4.23.22 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Crystallography is frequently used as follow-up method to validate hits identified by biophysical screening cascades. The capacity of crystallography to directly screen fragment libraries is often underestimated, due to its supposed low-throughput and need for high-quality crystals. We applied crystallographic fragment screening to map the protein-binding site of the aspartic protease endothiapepsin by individual soaking experiments. Here, we report on 41 fragments binding to the catalytic dyad and adjacent specificity pockets. The analysis identifies already known warheads but also reveals hydrazide, pyrazole, or carboxylic acid fragments as novel functional groups binding to the dyad. A remarkable swapping of the S1 and S1' pocket between structurally related fragments is explained by either steric demand, required displacement of a well-bound water molecule, or changes of trigonal-planar to tetrahedral geometry of an oxygen functional group in a side chain. Some warheads simultaneously occupying both S1 and S1' are promising starting points for fragment-growing strategies. 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 SG, Fu K, Stieler M, Ehrmann FR, Metz A, Rickmeyer T, Betz M, Winquist J, Park AY, Huschmann FU, Weiss MS, Mueller U, Heine A, Klebe G J Med Chem. 2016 Nov 10;59(21):9743-9759. doi: 10.1021/acs.jmedchem.6b01195. Epub, 2016 Oct 28. PMID:27726357 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA