7ov3

Crystal structure of pig purple acid phosphatase in complex with Maybridge fragment CC063346, dimethyl sulfoxide and citrate

spinqualitylabelsall models 7ov3, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: CIT, CL, DMS, EDO, FE, GOL, NA, NAG, PGE, PO4, R2J Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Metallohydrolases form a large group of enzymes that have fundamental importance in a broad range of biological functions. Among them, the purple acid phosphatases (PAPs) have gained attention due to their crucial role in the acquisition and use of phosphate by plants and also as a promising target for novel treatments of bone-related disorders and cancer. To date, no crystal structure of a mammalian PAP with drug-like molecules bound near the active site is available. Herein, we used a fragment-based design approach using structures of a mammalian PAP in complex with the Maybridge(TM) fragment CC063346, the amino acid L-glutamine and the buffer molecule HEPES, as well as various solvent molecules to guide the design of highly potent and efficient mammalian PAP inhibitors. These inhibitors have improved aqueous solubility when compared to the clinically most promising PAP inhibitors available to date. Furthermore, drug-like fragments bound in newly discovered binding sites mapped out additional scaffolds for further inhibitor discovery, as well as scaffolds for the design of inhibitors with novel modes of action. Rational Design of Potent Inhibitors of a Metallohydrolase Using a Fragment-Based Approach.,Feder D, Mohd-Pahmi SH, Hussein WM, Guddat LW, McGeary RP, Schenk G ChemMedChem. 2021 Nov 5;16(21):3342-3359. doi: 10.1002/cmdc.202100486. Epub 2021 , Sep 1. PMID:34331400 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Acid phosphatase 3D structures

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