7TBD
Crystal structure of Plasmepsin X from Plasmodium vivax in complex with WM382
Summary for 7TBD
| Entry DOI | 10.2210/pdb7tbd/pdb |
| Descriptor | Plasmepsin X, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total) |
| Functional Keywords | aspartyl protease, hydrolase |
| Biological source | Plasmodium vivax (malaria parasite P. vivax) |
| Total number of polymer chains | 2 |
| Total formula weight | 87432.07 |
| Authors | Hodder, A.N.,Christensen, J.B.,Scally, S.W.,Cowman, A.F. (deposition date: 2021-12-21, release date: 2022-05-04, Last modification date: 2024-11-06) |
| Primary citation | Hodder, A.N.,Christensen, J.,Scally, S.,Triglia, T.,Ngo, A.,Birkinshaw, R.W.,Bailey, B.,Favuzza, P.,Dietrich, M.H.,Tham, W.H.,Czabotar, P.E.,Lowes, K.,Guo, Z.,Murgolo, N.,Lera Ruiz, M.,McCauley, J.A.,Sleebs, B.E.,Olsen, D.,Cowman, A.F. Basis for drug selectivity of plasmepsin IX and X inhibition in Plasmodium falciparum and vivax. Structure, 30:947-, 2022 Cited by PubMed Abstract: Plasmepsins IX (PMIX) and X (PMX) are essential aspartyl proteases for Plasmodium spp. egress, invasion, and development. WM4 and WM382 inhibit PMIX and PMX in Plasmodium falciparum and P. vivax. WM4 inhibits PMX, while WM382 is a dual inhibitor of PMIX and PMX. To understand their function, we identified protein substrates. Enzyme kinetic and structural analyses identified interactions responsible for drug specificity. PMIX and PMX have similar substrate specificity; however, there are distinct differences for peptide and protein substrates. Differences in WM4 and WM382 binding for PMIX and PMX map to variations in the S' region and engagement of the active site S3 pocket. Structures of PMX reveal interactions and mechanistic detail of drug binding important for development of clinical candidates against these targets. PubMed: 35460613DOI: 10.1016/j.str.2022.03.018 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.22 Å) |
Structure validation
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