5MRO
Arabidopsis thaliana IspD Glu258Ala mutant in complex with Azolopyrimidine (1)
Summary for 5MRO
| Entry DOI | 10.2210/pdb5mro/pdb |
| Related | 1W77 2YC5 4NAK |
| Descriptor | 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase, chloroplastic, Azolopyrimidine, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (7 entities in total) |
| Functional Keywords | herbicide, anti-infectives, drug discovery, allosteric inhibition, mutant, transferase |
| Biological source | Arabidopsis thaliana (Mouse-ear cress) |
| Cellular location | Plastid, chloroplast stroma : P69834 |
| Total number of polymer chains | 1 |
| Total formula weight | 26190.36 |
| Authors | Schwab, A.,Illarionov, B.,Frank, A.,Kunfermann, A.,Seet, M.,Bacher, A.,Witschel, M.,Fischer, M.,Groll, M.,Diederich, F. (deposition date: 2016-12-23, release date: 2017-07-19, Last modification date: 2024-01-17) |
| Primary citation | Schwab, A.,Illarionov, B.,Frank, A.,Kunfermann, A.,Seet, M.,Bacher, A.,Witschel, M.C.,Fischer, M.,Groll, M.,Diederich, F. Mechanism of Allosteric Inhibition of the Enzyme IspD by Three Different Classes of Ligands. ACS Chem. Biol., 12:2132-2138, 2017 Cited by PubMed Abstract: Enzymes of the nonmevalonate pathway of isoprenoid biosynthesis are attractive targets for the development of herbicides and drugs against infectious diseases. While this pathway is essential for many pathogens and plants, mammals do not depend on it for the synthesis of isoprenoids. IspD, the third enzyme of the nonmevalonate pathway, is unique in that it has an allosteric regulatory site. We elucidated the binding mode of phenylisoxazoles, a new class of allosteric inhibitors. Allosteric inhibition is effected by large conformational changes of a loop region proximal to the active site. We investigated the different roles of residues in this loop by mutation studies and identified repulsive interactions with Asp291 and Asp292 to be responsible for inhibition. Crystallographic data and the response of mutant enzymes to three different classes of allosteric inhibitors provide an in-depth understanding of the allosteric mechanism. The obtained mutant enzymes show selective resistance to allosteric inhibitors and provide conceptually valuable information for future engineering of herbicide-resistant crops. We found that the isoprenoid precursors IPP and DMAPP are natural inhibitors of Arabidopsis thaliana IspD; however, they do not seem to bind to the allosteric site. PubMed: 28686408DOI: 10.1021/acschembio.7b00004 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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