3SZO

IspH:HMBPP complex after 3 minutes X-ray pre-exposure

3SZO の概要

• エントリーDOI: 10.2210/pdb3szo/pdb
• 関連するPDBエントリー: 3DNF 3F7T 3SZL 3SZU 3T0F 3T0G
• 分子名称: 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)
• 機能のキーワード: 4fe-4s iron-sulfur cluster, conserved cysteine, ipp and dmapp production final step, non-mevalonate pathway, substrate hmbpp, alternate conformations, oxidoreductase
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 73673.53

構造登録者

Span, I.,Graewert, T.,Bacher, A.,Eisenreich, W.,Groll, M. (登録日: 2011-07-19, 公開日: 2011-11-30, 最終更新日: 2023-09-13)

主引用文献

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

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: 22137895
DOI: 10.1016/j.jmb.2011.11.033

実験手法

X-RAY DIFFRACTION (1.6 Å)