A Mycobacterium tuberculosis ligand-binding Mn/Fe protein reveals a new cofactor in a remodeled R2-protein scaffold
A Mycobacterium tuberculosis ligand-binding Mn/Fe protein reveals a new cofactor in a remodeled R2-protein scaffold
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DOI：
10.1073/pnas.0812971106
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发表时间：
2009-04-07
影响因子：
11.1
通讯作者：
Hoegbom, Martin
中科院分区：
文献类型：
--
作者：
Andersson, Charlotta S.;Hoegbom, Martin
沙眼衣原体R2c是最近发现的一组核糖核苷酸还原酶R2蛋白的原型，该蛋白使用异核Mn/Fe氧化还原辅助因子产生和储存自由基。在这里，我们发现结核分枝杆菌蛋白Rv0233，一个R2同源物和一个潜在的毒力因子，含有异核锰/铁羧酸辅助因子，但表现出R2蛋白支架的剧烈重塑为配体结合氧化酶。异质双核辅助因子的第一个结构表征表明，尽管配位残基排列对称，但该位点对各自位置的锰和铁具有高度特异性。在这个蛋白质支架中，Mn/Fe辅助因子支持强有力的2电子氧化，这是在活性位点前所未有的酪氨酸-缬氨酸交联所揭示的。这种披着羊皮的狼在R2同源物中定义了一个独特的功能群，可能代表了R2s和细菌多组分单加氧酶的进化祖先的结构和功能对应物。
Chlamydia trachomatis R2c is the prototype for a recently discovered group of ribonucleotide reductase R2 proteins that use a heterodinuclear Mn/Fe redox cofactor for radical generation and storage. Here, we show that the Mycobacterium tuberculosis protein Rv0233, an R2 homologue and a potential virulence factor, contains the heterodinuclear manganese/iron-carboxylate cofactor but displays a drastic remodeling of the R2 protein scaffold into a ligand-binding oxidase. The first structural characterization of the heterodinuclear cofactor shows that the site is highly specific for manganese and iron in their respective positions despite a symmetric arrangement of coordinating residues. In this protein scaffold, the Mn/Fe cofactor supports potent 2-electron oxidations as revealed by an unprecedented tyrosine-valine crosslink in the active site. This wolf in sheep's clothing defines a distinct functional group among R2 homologues and may represent a structural and functional counterpart of the evolutionary ancestor of R2s and bacterial multicomponent monooxygenases.