7OV8
Crystal structure of pig purple acid phosphatase in complex with 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) and glycerol
Summary for 7OV8
| Entry DOI | 10.2210/pdb7ov8/pdb |
| Related | 7OV2 7OV3 |
| Descriptor | Tartrate-resistant acid phosphatase type 5, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, ... (10 entities in total) |
| Functional Keywords | purple acid phosphatase, metallohydrolases, osteoporosis, fragment-based drug design, metal binding protein, hydrolase |
| Biological source | Sus scrofa (Pig) |
| Total number of polymer chains | 1 |
| Total formula weight | 40911.04 |
| Authors | Feder, D.,McGeary, R.P.,Guddat, L.W.,Schenk, G. (deposition date: 2021-06-14, release date: 2022-03-23, Last modification date: 2024-10-09) |
| Primary citation | Feder, D.,Mohd-Pahmi, S.H.,Hussein, W.M.,Guddat, L.W.,McGeary, R.P.,Schenk, G. Rational Design of Potent Inhibitors of a Metallohydrolase Using a Fragment-Based Approach. Chemmedchem, 16:3342-3359, 2021 Cited by PubMed Abstract: 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 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. PubMed: 34331400DOI: 10.1002/cmdc.202100486 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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