7ZOG
Crystal structure of Cryptosporidium parvum -Plasmodium falciparum mutant lysyl tRNA synthetase in complex with inhibitor
Summary for 7ZOG
| Entry DOI | 10.2210/pdb7zog/pdb |
| Descriptor | Lysine-tRNA ligase, LYSINE, 8-[[4-[2-[2-[2-[2-[(azanylidene-$l^{4}-azanylidene)amino]ethoxy]ethoxy]ethoxy]ethylcarbamoyl]phenyl]sulfonylamino]-~{N}-(cyclohexylmethyl)-6-fluoranyl-4-oxidanylidene-chromene-2-carboxamide, ... (5 entities in total) |
| Functional Keywords | trna binding, ligase |
| Biological source | Cryptosporidium parvum Iowa II |
| Total number of polymer chains | 4 |
| Total formula weight | 249812.81 |
| Authors | Dawson, A.,Wyllie, S. (deposition date: 2022-04-25, release date: 2022-09-07, Last modification date: 2024-06-19) |
| Primary citation | Milne, R.,Wiedemar, N.,Corpas-Lopez, V.,Moynihan, E.,Wall, R.J.,Dawson, A.,Robinson, D.A.,Shepherd, S.M.,Smith, R.J.,Hallyburton, I.,Post, J.M.,Dowers, K.,Torrie, L.S.,Gilbert, I.H.,Baragana, B.,Patterson, S.,Wyllie, S. Toolkit of Approaches To Support Target-Focused Drug Discovery for Plasmodium falciparum Lysyl tRNA Synthetase. Acs Infect Dis., 8:1962-1974, 2022 Cited by PubMed Abstract: There is a pressing need for new medicines to prevent and treat malaria. Most antimalarial drug discovery is reliant upon phenotypic screening. However, with the development of improved target validation strategies, target-focused approaches are now being utilized. Here, we describe the development of a toolkit to support the therapeutic exploitation of a promising target, lysyl tRNA synthetase (KRS). The toolkit includes resistant mutants to probe resistance mechanisms and on-target engagement for specific chemotypes; a hybrid KRS protein capable of producing crystals suitable for ligand soaking, thus providing high-resolution structural information to guide compound optimization; chemical probes to facilitate pulldown studies aimed at revealing the full range of specifically interacting proteins and thermal proteome profiling (TPP); as well as streamlined isothermal TPP methods to provide unbiased confirmation of on-target engagement within a biologically relevant milieu. This combination of tools and methodologies acts as a template for the development of future target-enabling packages. PubMed: 36037410DOI: 10.1021/acsinfecdis.2c00364 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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