Diphthamide biosynthesis requires an organic radical generated by an iron-sulphur enzyme.
Diphthamide biosynthesis requires an organic radical generated by an iron-sulphur enzyme.
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作者：
古细菌和真核生物的翻译延伸因子2含有一种独特的翻译后修饰的组氨酸残基，称为“双酞胺”，是白喉毒素的靶标。二苯二胺的生物合成分为三步，第一步是组氨酸残基与s -腺苷蛋氨酸（SAM）的3-氨基-3-羧基之间形成C-C键。然而，生物合成的细节仍然未知。在这里，我们提出了结构和生化证据表明，在古细菌堀koshii焦球菌中，双酞胺生物合成的第一步使用了一种新的铁硫簇酶Dph2。Dph2是一个同型二聚体，每个单体含有一个[4Fe-4S]簇。生化数据表明，与自由基SAM超家族中的酶不同，Dph2不会形成典型的5 ' -脱氧腺苷基自由基。相反，它会破坏SAM的c - γ，Met-S键，生成一个3-氨基-3-羧基丙基自由基。这项工作表明，博氏焦球菌Dph2代表了一种新的sam依赖[4Fe-4S]含酶，催化前所未有的化学反应。
Archaeal and eukaryotic translation elongation factor 2 contain a unique posttranslationally modified histidine residue called “diphthamide”, the target of diphtheria toxin. The biosynthesis of diphthamide were proposed to involve three steps, with the first step being the formation of a C-C bond between the histidine residue and the 3-amino-3-carboxypropyl group of S-adenosylmethionine (SAM). However, details of the biosynthesis have remained unknown. Here we present structural and biochemical evidence showing that the first step of diphthamide biosynthesis in the archaeon Pyrococcus horikoshii uses a novel iron-sulfur cluster enzyme, Dph2. Dph2 is a homodimer and each monomer contains a [4Fe-4S] cluster. Biochemical data suggest that unlike the enzymes in the radical SAM superfamily, Dph2 does not form the canonical 5′-deoxyadenosyl radical. Instead, it breaks the Cγ,Met-S bond of SAM and generates a 3-amino-3-carboxylpropyl radical. This work suggests that Pyrococcus horikoshii Dph2 represents a novel SAM-dependent [4Fe-4S]-containing enzyme that catalyzes unprecedented chemistry.
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影响因子：
14.8
作者：
Chatterjee, Abhishek;Li, Yue;Zhang, Yang;Grove, Tyler L.;Lee, Michael;Krebs, Carsten;Booker, Squire J.;Begley, Tadhg P.;Ealick, Steven E.
通讯作者：
Ealick, Steven E.
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
5.3
作者：
MOEHRING, TJ;DANLEY, DE;MOEHRING, JM
通讯作者：
MOEHRING, JM
影响因子：
64.8
作者：
Gavin, AC;Aloy, P;Superti-Furga, G
通讯作者：
Superti-Furga, G
DOI：
10.1107/s0907444998003254
发表时间：
1998-09-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Brunger, AT;Adams, PD;Warren, GL
通讯作者：
Warren, GL