Structure of (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate reductase, the terminal enzyme of the non-mevalonate pathway.
Structure of (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate reductase, the terminal enzyme of the non-mevalonate pathway.
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DOI：
10.1021/ja806668q
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发表时间：
2008-12-24
影响因子：
15
通讯作者：
Ermler, Ulrich
中科院分区：
文献类型：
--
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
分子进化为类异戊二烯生物合成进化出两条代谢途径：甲氧戊酸途径和2-C-甲基-D-赤藓糖醇-4-磷酸(MEP)途径。大多数致病细菌和一些寄生原虫(包括疟疾寄生虫、恶性疟原虫)以及植物都使用MEP途径，但动物中不存在。MEP途径的末端反应是由(E)-4-羟基-3-甲基-2-烯基二磷酸(HMBPP)还原酶(LytB)催化的，LytB是一种将HMBPP转化为异戊二磷酸(IPP)和二甲基烯丙基二磷酸(DMAPP)的酶。在这里，我们介绍了Aquifex aeolicus LytB的结构，分辨率为1.65？该蛋白质采用三叶草或三叶状结构，二聚体中的每个单体都包含三个α/β结构域，包围着连接到Cys13、Cys96和Cys193的中心[Fe3S4]簇。两个高度保守的His(His 42和His 124)和一个完全保守的Glu(Glu126)位于同一个中心位置，被认为参与了配体的结合和催化。底物的进入被认为是从蛋白质的正面发生的，HMBPP的二磷酸与两个His结合，HMBPP的4OH结合到第四个铁被认为存在于活化的簇中，而Glu126提供形成IPP/DMAPP所需的质子。
Molecular evolution has evolved two metabolic routes for isoprenoid biosynthesis: the mevalonate and the 2-C-methyl-d-erythritol-4-phosphate (MEP) pathway. The MEP pathway is used by most pathogenic bacteria and some parasitic protozoa (including the malaria parasite,Plasmodium falciparum) as well as by plants, but is not present in animals. The terminal reaction of the MEP pathway is catalyzed by (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate (HMBPP) reductase (LytB), an enzyme that converts HMBPP into isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Here, we present the structure ofAquifex aeolicusLytB, at 1.65 Å resolution. The protein adopts a cloverleaf or trefoil-like structure with each monomer in the dimer containing three α/β domains surrounding a central [Fe3S4] cluster ligated to Cys13, Cys96, and Cys193. Two highly conserved His (His 42 and His 124) and a totally conserved Glu (Glu126) are located in the same central site and are proposed to be involved in ligand binding and catalysis. Substrate access is proposed to occur from the front-side face of the protein, with the HMBPP diphosphate binding to the two His and the 4OH of HMBPP binding to the fourth iron thought to be present in activated clusters, while Glu126 provides the protons required for IPP/DMAPP formation.
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影响因子：
5.8
作者：
Cuff, JA;Clamp, ME;Barton, GJ
通讯作者：
Barton, GJ
影响因子：
56.9
作者：
Jomaa, H;Wiesner, J;Beck, E
通讯作者：
Beck, E
DOI：
10.1073/pnas.182412599
发表时间：
2002-09-17
影响因子：
11.1
作者：
Adam, P;Hecht, S;Rohdich, F
通讯作者：
Rohdich, F
DOI：
10.1073/pnas.94.24.12857
发表时间：
1997-11-25
影响因子：
11.1
作者：
Sprenger, GA;Schorken, U;Sahm, H
通讯作者：
Sahm, H
影响因子：
2.1
作者：
HORBACH, S;SAHM, H;WELLE, R
通讯作者：
WELLE, R