6R5H
Major aspartyl peptidase 1 from C. neoformans
Summary for 6R5H
| Entry DOI | 10.2210/pdb6r5h/pdb |
| Descriptor | Endopeptidase, PENTAETHYLENE GLYCOL, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (11 entities in total) |
| Functional Keywords | aspartyl protease, secreted, cryptococcus neoformans, hydrolase |
| Biological source | Cryptococcus neoformans var. grubii serotype A (strain H99 / ATCC 208821 / CBS 10515 / FGSC 9487) |
| Total number of polymer chains | 1 |
| Total formula weight | 39113.55 |
| Authors | Krystufek, R.,Sacha, P.,Brynda, J.,Konvalinka, J. (deposition date: 2019-03-25, release date: 2021-04-07, Last modification date: 2024-11-13) |
| Primary citation | Krystufek, R.,Sacha, P.,Starkova, J.,Brynda, J.,Hradilek, M.,Tloust'ova, E.,Grzymska, J.,Rut, W.,Boucher, M.J.,Drag, M.,Majer, P.,Hajek, M.,Rezacova, P.,Madhani, H.D.,Craik, C.S.,Konvalinka, J. Re-emerging Aspartic Protease Targets: Examining Cryptococcus neoformans Major Aspartyl Peptidase 1 as a Target for Antifungal Drug Discovery. J.Med.Chem., 64:6706-6719, 2021 Cited by PubMed Abstract: Cryptococcosis is an invasive infection that accounts for 15% of AIDS-related fatalities. Still, treating cryptococcosis remains a significant challenge due to the poor availability of effective antifungal therapies and emergence of drug resistance. Interestingly, protease inhibitor components of antiretroviral therapy regimens have shown some clinical benefits in these opportunistic infections. We investigated Major aspartyl peptidase 1 (May1), a secreted protease, as a possible target for the development of drugs that act against both fungal and retroviral aspartyl proteases. Here, we describe the biochemical characterization of May1, present its high-resolution X-ray structure, and provide its substrate specificity analysis. Through combinatorial screening of 11,520 compounds, we identified a potent inhibitor of May1 and HIV protease. This dual-specificity inhibitor exhibits antifungal activity in yeast culture, low cytotoxicity, and low off-target activity against host proteases and could thus serve as a lead compound for further development of May1 and HIV protease inhibitors. PubMed: 34006103DOI: 10.1021/acs.jmedchem.0c02177 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.75 Å) |
Structure validation
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