3SZL
IspH:Ligand Mutants - wt 70sec
Summary for 3SZL
| Entry DOI | 10.2210/pdb3szl/pdb |
| Related | 3DNF 3F7T 3SZO 3SZU 3T0F 3T0G |
| Descriptor | 4-hydroxy-3-methylbut-2-enyl diphosphate reductase, IRON/SULFUR CLUSTER, (2E)-4-hydroxy-3-methylbut-2-en-1-yl trihydrogen diphosphate, ... (4 entities in total) |
| Functional Keywords | 4fe-4s iron-sulfur cluster, conserved cysteine, induced fit mechanism, ipp and dmapp production final step, non-mevalonate pathway, substrate hmbpp, oxidoreductase |
| Biological source | Escherichia coli |
| Total number of polymer chains | 2 |
| Total formula weight | 73673.53 |
| Authors | Span, I.,Graewert, T.,Bacher, A.,Eisenreich, W.,Groll, M. (deposition date: 2011-07-19, release date: 2011-11-30, Last modification date: 2023-09-13) |
| Primary citation | Span, I.,Grawert, T.,Bacher, A.,Eisenreich, W.,Groll, M. Crystal Structures of Mutant IspH Proteins Reveal a Rotation of the Substrate's Hydroxymethyl Group during Catalysis. J.Mol.Biol., 416:1-9, 2012 Cited by PubMed Abstract: Isoprenoids derive from two universal precursors, isopentenyl diphosphate and dimethylallyl diphosphate, which in most human pathogens are synthesized in the deoxyxylulose phosphate pathway. The last step of this pathway is the conversion of (E)-1-hydroxy-2-methylbut-2-enyl-4-diphosphate into a mixture of isopentenyl diphosphate and dimethylallyl diphosphate catalyzed by the iron-sulfur protein IspH. The crystal structures reported here of the IspH mutant proteins T167C, E126D and E126Q reveal an alternative substrate conformation compared to the wild-type structure. Thus, the previously observed alkoxide complex decomposes, and the substrate's hydroxymethyl group rotates to interact with Glu126. The carboxyl group of Glu126 then donates a proton to the hydroxyl group to enable water elimination. The structural and functional studies provide further knowledge of the IspH reaction mechanism, which opens up new routes to inhibitor design against malaria and tuberculosis. PubMed: 22137895DOI: 10.1016/j.jmb.2011.11.033 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.6 Å) |
Structure validation
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