Summary for 9JOA
| Entry DOI | 10.2210/pdb9joa/pdb |
| Related | 9JOB |
| Descriptor | 1-deoxy-D-xylulose 5-phosphate reductoisomerase, apicoplastic, MANGANESE (II) ION, [(1~{S})-4-oxidanylidene-4-[oxidanyl(3-phenylpropyl)amino]-1-phenyl-butyl]phosphonic acid, ... (6 entities in total) |
| Functional Keywords | malaria, isomerase |
| Biological source | Plasmodium falciparum HB3 |
| Total number of polymer chains | 2 |
| Total formula weight | 112828.26 |
| Authors | |
| Primary citation | Abdullaziz, M.A.,Takada, S.,Illarionov, B.,Pessanha de Carvalho, L.,Sakamoto, Y.,Hoefmann, S.,Knak, T.,Kiffe-Delf, A.L.,Mazzone, F.,Pfeffer, K.,Kalscheuer, R.,Bacher, A.,Held, J.,Fischer, M.,Tanaka, N.,Kurz, T. Reverse N-Substituted Hydroxamic Acid Derivatives of Fosmidomycin Target a Previously Unknown Subpocket of 1-Deoxy-d-xylulose 5-Phosphate Reductoisomerase (DXR) ACS Infect Dis, 10:1739-1752, 2024 Cited by PubMed Abstract: Reverse analogs of the phosphonohydroxamic acid antibiotic fosmidomycin are potent inhibitors of the nonmevalonate isoprenoid biosynthesis enzyme 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR, IspC) of . Some novel analogs with large phenylalkyl substituents at the hydroxamic acid nitrogen exhibit nanomolar DXR inhibition and potent growth inhibition of parasites coupled with good parasite selectivity. X-ray crystallographic studies demonstrated that the -phenylpropyl substituent of the newly developed lead compound is accommodated in a subpocket within the DXR catalytic domain but does not reach the NADPH binding pocket of the -terminal domain. As shown for reverse carba and thia analogs, DXR selectively binds the -enantiomer of the new lead compound. In addition, some representatives of the novel inhibitor subclass are nanomolar DXR inhibitors, whereas the inhibition of DXR is considerably weaker. PubMed: 38647213DOI: 10.1021/acsinfecdis.4c00100 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.5 Å) |
Structure validation
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