6NXG
Crystal structure of glycylpeptide N-tetradecanoyltransferase from Plasmodium vivax in complex with inhibitor 303a
Summary for 6NXG
| Entry DOI | 10.2210/pdb6nxg/pdb |
| Descriptor | Glycylpeptide N-tetradecanoyltransferase, MAGNESIUM ION, CHLORIDE ION, ... (9 entities in total) |
| Functional Keywords | transferase, structural genomics, seattle structural genomics center for infectious disease, ssgcid, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Plasmodium vivax (strain Salvador I) |
| Total number of polymer chains | 3 |
| Total formula weight | 146099.08 |
| Authors | Staker, B.L.,Mayclin, S.,Seattle Structural Genomics Center for Infectious Disease (SSGCID) (deposition date: 2019-02-08, release date: 2020-01-01, Last modification date: 2023-10-11) |
| Primary citation | Harupa, A.,De Las Heras, L.,Colmenarejo, G.,Lyons-Abbott, S.,Reers, A.,Caballero Hernandez, I.,Chung, C.W.,Charter, D.,Myler, P.J.,Fernandez-Menendez, R.M.,Calderon, F.,Palomo, S.,Rodriguez, B.,Berlanga, M.,Herreros-Aviles, E.,Staker, B.L.,Fernandez Alvaro, E.,Kaushansky, A. Identification of Selective Inhibitors ofPlasmodiumN-Myristoyltransferase by High-Throughput Screening. J.Med.Chem., 63:591-600, 2020 Cited by PubMed Abstract: New drugs that target species, the causative agents of malaria, are needed. The enzyme -myristoyltransferase (NMT) is an essential protein, which catalyzes the myristoylation of protein substrates, often to mediate membrane targeting. We screened ∼1.8 million small molecules for activity against () NMT. Hits were triaged based on potency and physicochemical properties and further tested against and () NMTs. We assessed the activity of hits against human NMT1 and NMT2 and discarded compounds with low selectivity indices. We identified 23 chemical classes specific for the inhibition of NMTs over human NMTs, including multiple novel scaffolds. Cocrystallization of NMT with one compound revealed peptide binding pocket binding. Other compounds show a range of potential modes of action. Our data provide insight into the activity of a collection of selective inhibitors of NMT and serve as a starting point for subsequent medicinal chemistry efforts. PubMed: 31850752DOI: 10.1021/acs.jmedchem.9b01343 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.6 Å) |
Structure validation
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