Biosynthesis of isoprene units: Mössbauer spectroscopy of substrate and inhibitor binding to the [4Fe-4S] cluster of the LytB/IspH enzyme.
Biosynthesis of isoprene units: Mössbauer spectroscopy of substrate and inhibitor binding to the [4Fe-4S] cluster of the LytB/IspH enzyme.
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DOI：
10.1002/anie.201104562
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发表时间：
2011-12-09
影响因子：
16.6
通讯作者：
Seemann, Myriam
中科院分区：
文献类型：
--
作者：
Ahrens-Botzong, Annegret;Janthawornpong, Karnjapan;Wolny, Juliusz A.;Tambou, Erasmienne Ngouamegne;Rohmer, Michel;Krasutsky, Sergiy;Poulter, C. Dale;Schuenemann, Volker;Seemann, Myriam
许多细菌和恶性疟原虫中的类异戊二烯生物合成是根据甲基赤藓糖醇磷酸 (MEP) 途径进行的，[1] 是甲羟戊酸途径的替代途径。 [2] MEP 途径是开发新型抗菌药物的重要靶点，因为它对微生物至关重要，但在人类中却缺乏。[3]在该生物合成路线的最后一步（方案1）中，1-羟基-2-甲基-2-丁烯基4-二磷酸酯（HMBPP，1）被转化为异戊烯基焦磷酸酯（IPP）和二甲基烯丙基焦磷酸酯（DMAPP）的混合物，它们都是类异戊二烯的前体。该反应由 LytB/IspH 蛋白特有的 [4Fe-4S] 中心催化。[4]LytB 的分子量为 72kDa，是同型二聚体。它包含对 O2 高度敏感的 [4Fe-4S] 2+ 簇，该簇具有抗磁性，因此在电子顺磁共振 (EPR) 谱中没有显示任何信号。 [5]场相关 Mçssbauer 光谱表明，无底物形式的 LytB [4Fe-4S] 2+ 簇中的四个铁中心与传统铁氧还蛋白型 [4Fe-4S] 2+ 簇中的四个铁中心不同。 [6]相反，其中一个铁位点具有异构体位移 (δ= 0.89 mms±1)，在实验误差范围内，该异构体位移与柠檬酸结合形式的乌头酸酶中不寻常的第四个铁位点的异构体位移相同。 [4]因此，得出的结论是，该特殊铁位点的配位层包含来自以下元素的三个无机硫原子：
The biosynthesis of isoprenoids in many bacteria and in the malaria parasite Plasmodium falciparum occurs according to the methylerythritol phosphate (MEP) pathway,[1] an alternative to the mevalonate pathway.[2] The MEP pathway is a valuable target for the development of new antimicrobial agents, as it is essential for microorganisms and absent in humans.[3] In the last step of this biosynthetic route (Scheme 1), 1-hydroxy-2-methyl-2-butenyl 4-diphosphate (HMBPP, 1) is converted into a mixture of isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), which are both precursors of isoprenoids. This reaction is catalyzed by a peculiar [4Fe-4S] center of the LytB/IspH protein.[4]LytB has a molecular weight of 72kDa and is a homodimer. It contains a highly O2-sensitive [4Fe-4S] 2+ cluster, which is diamagnetic and therefore shows no signal in the electron paramagnetic resonance (EPR) spectrum.[5] Field-dependent Mçssbauer spectroscopy indicated that the four iron centers in the [4Fe-4S] 2+ cluster of LytB in its substrate-free form are not equivalent as in conventional ferredoxin-type [4Fe-4S] 2+ clusters.[6] Instead, one of the iron sites has an isomer shift (δ= 0.89 mmsÀ1) that is identical within experimental error to that of an unusual fourth iron site in the citrate-bound form of aconitase.[4] Accordingly, it was concluded that the coordination sphere of this special iron site comprises three inorganic sulfur atoms from the
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影响因子：
16.6
作者：
Graewert, Tobias;Rohdich, Felix;Groll, Michael
通讯作者：
Groll, Michael
影响因子：
15
作者：
Xiao, Youli;Zhao, Zongbao K.;Liu, Pinghua
通讯作者：
Liu, Pinghua
DOI：
10.1073/pnas.0913045107
发表时间：
2010-01-19
影响因子：
11.1
作者：
Graewert, Tobias;Span, Ingrid;Groll, Michael
通讯作者：
Groll, Michael
影响因子：
15
作者：
Rekittke, Ingo;Wiesner, Jochen;Roehrich, Rene;Demmer, Ulrike;Warkentin, Eberhard;Xu, Weiya;Troschke, Kathrin;Hintz, Martin;No, Joo Hwan;Duin, Evert C.;Oldfield, Eric;Jomaa, Hassan;Ermler, Ulrich
通讯作者：
Ermler, Ulrich
影响因子：
15
作者：
CIURLI, S;CARRIE, M;HOLM, RH
通讯作者：
HOLM, RH