5CBM
Crystal structure of PfA-M17 with virtual ligand inhibitor
Summary for 5CBM
| Entry DOI | 10.2210/pdb5cbm/pdb |
| Related | 3KQZ |
| Descriptor | M17 family aminopeptidase, CARBONATE ION, ZINC ION, ... (8 entities in total) |
| Functional Keywords | m17 leucyl-aminopeptidase, protease, inhibitor, hydroxamic acid, hydrolase |
| Biological source | Plasmodium falciparum Vietnam Oak-Knoll (FVO) |
| Total number of polymer chains | 12 |
| Total formula weight | 705396.14 |
| Authors | Ruggeri, C.,Drinkwater, N.,McGowan, S. (deposition date: 2015-07-01, release date: 2015-10-07, Last modification date: 2024-01-10) |
| Primary citation | Ruggeri, C.,Drinkwater, N.,Sivaraman, K.K.,Bamert, R.S.,McGowan, S.,Paiardini, A. Identification and Validation of a Potent Dual Inhibitor of the P. falciparum M1 and M17 Aminopeptidases Using Virtual Screening. Plos One, 10:e0138957-e0138957, 2015 Cited by PubMed Abstract: The Plasmodium falciparum PfA-M1 and PfA-M17 metalloaminopeptidases are validated drug targets for the discovery of antimalarial agents. In order to identify dual inhibitors of both proteins, we developed a hierarchical virtual screening approach, followed by in vitro evaluation of the highest scoring hits. Starting from the ZINC database of purchasable compounds, sequential 3D-pharmacophore and molecular docking steps were applied to filter the virtual 'hits'. At the end of virtual screening, 12 compounds were chosen and tested against the in vitro aminopeptidase activity of both PfA-M1 and PfA-M17. Two molecules showed significant inhibitory activity (low micromolar/nanomolar range) against both proteins. Finally, the crystal structure of the most potent compound in complex with both PfA-M1 and PfA-M17 was solved, revealing the binding mode and validating our computational approach. PubMed: 26406322DOI: 10.1371/journal.pone.0138957 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
Download full validation report
