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首页> 外文期刊>Biochemistry >Molecular Architecture of a C-3′-Methyltransferase Involved in the Biosynthesis of d-Tetronitrose
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Molecular Architecture of a C-3′-Methyltransferase Involved in the Biosynthesis of d-Tetronitrose

机译：C-3'-甲基转移酶参与d-四亚硝基酶生物合成的分子结构

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S-Adenosylmethionine (SAM)-dependent methyltransferases are involved in a myriad of bio-nlogical processes, including signal transduction, chromatin repair, metabolism, and biosyntheses, amongnothers. Here we report the high-resolution structure of a novel C-30n-methyltransferase involved in the produc-ntion of D-tetronitrose, an unusual sugar found attached to the antitumor agent tetrocarcin A or the antibioticnkijanimicin. Specifically, this enzyme, referred to as TcaB9 and cloned from Micromonospora chalcea,ncatalyzes the conversion of dTDP-3-amino-2,3,6-trideoxy-4-keto-D-glucose to dTDP-3-amino-2,3,6-tri-ndeoxy-4-keto-3-methyl-D-glucose. For this analysis, two structures were determined to 1.5 A resolution:none in which the enzyme was crystallized in the presence of SAM and dTMP and the other with the proteinncomplexed to S-adenosylhomocysteine and its dTDP-linked sugar product. The overall fold of thenmonomeric enzyme can be described in terms of three domains. The N-terminal domain harbors the bindingnsite for a zinc ion that is ligated by four cysteines. The middle domain adopts the canonical “SAM-binding”nfold with a seven-stranded mixed β-sheet flanked on either side by three R-helices. This domain is responsiblenfor anchoring the SAM cofactor to the protein. Strikingly, the C-terminal domain also contains a seven-nstranded β-sheet, and it appears to be related to the middle domain by an approximate 2-fold rotational axis,nthus suggesting TcaB9 arose via gene duplication. Key residues involved in sugar binding include His 181,nGlu 224, His 225, and Tyr 222. Their possible roles in catalysis are discussed.
机译：S-腺苷甲硫氨酸（SAM）依赖的甲基转移酶参与了众多的生物过程，包括信号转导，染色质修复，代谢和生物合成等。在这里，我们报道了一种新型的C-30n-甲基转移酶的高分辨率结构，该酶涉及D-四亚硝基酶的生产，D-四亚硝基酶是一种与抗肿瘤药tetrocarcin A或抗生素nkijanimicin相连的不寻常糖。具体地说，这种酶（称为TcaB9）是从小单孢菌（Micromonospora chalcea）克隆而来，它催化dTDP-3-amino-2,3,6-trideoxy-4-keto-D-glucose转化为dTDP-3-amino-2,3 ，6-三-脱氧-4-酮-3-甲基-D-葡萄糖。为了进行该分析，确定了两个结构，分辨率为1.5 A：无一个在SAM和dTMP存在的条件下使酶结晶，另一个结构使该蛋白与S-腺苷同型半胱氨酸及其dTDP连接的糖产物复合。单体酶的总体折叠可以用三个结构域来描述。 N-末端结构域包含由四个半胱氨酸连接的锌离子的结合位点。中间结构域采用规范的“ SAM结合”折叠，其七链混合β折叠在两侧均带有三个R螺旋。该结构域负责将SAM辅因子锚定至蛋白质。令人惊讶的是，C末端结构域还包含一个7个nstranded的β-折叠，并且似乎通过大约2倍的旋转轴与中间结构域相关，因此暗示TcaB9是通过基因复制产生的。与糖结合有关的关键残基包括His 181，nGlu 224，His 225和Tyr222。讨论了它们在催化中的可能作用。

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