1] Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [2] Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona, USA.
Nat Chem Biol. 2014 Feb;10(2):106-12. doi: 10.1038/nchembio.1426. Epub 2013 Dec 22.
7-carboxy-7-deazaguanine synthase (QueE) catalyzes a key S-adenosyl-L-methionine (AdoMet)- and Mg(2+)-dependent radical-mediated ring contraction step, which is common to the biosynthetic pathways of all deazapurine-containing compounds. QueE is a member of the AdoMet radical superfamily, which employs the 5'-deoxyadenosyl radical from reductive cleavage of AdoMet to initiate chemistry. To provide a mechanistic rationale for this elaborate transformation, we present the crystal structure of a QueE along with structures of pre- and post-turnover states. We find that substrate binds perpendicular to the [4Fe-4S]-bound AdoMet, exposing its C6 hydrogen atom for abstraction and generating the binding site for Mg(2+), which coordinates directly to the substrate. The Burkholderia multivorans structure reported here varies from all other previously characterized members of the AdoMet radical superfamily in that it contains a hypermodified (β6/α3) protein core and an expanded cluster-binding motif, CX14CX2C.
7-羧基-7-脱氮鸟嘌呤合酶（QueE）催化一个关键的 S-腺苷-L-甲硫氨酸（AdoMet）和 Mg（2+）依赖性自由基介导的环收缩步骤，这是所有含脱氮嘌呤化合物生物合成途径所共有的。QueE 是 AdoMet 自由基超家族的成员，它利用 AdoMet 还原裂解产生的 5'-脱氧腺苷基自由基引发化学反应。为了提供这种复杂转化的机制基础，我们呈现了 QueE 的晶体结构以及前和后周转状态的结构。我们发现底物垂直于 [4Fe-4S]结合的 AdoMet 结合，暴露出其 C6 氢原子供提取，并生成与 Mg（2+）配位的结合位点，Mg（2+）直接与底物配位。与所有以前表征的 AdoMet 自由基超家族成员不同，报道的伯克霍尔德菌多形菌结构含有一个超修饰的（β6/α3）蛋白核心和一个扩展的簇结合基序，CX14CX2C。
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