AdoMet radical proteins - from structure to evolution - alignment of divergent protein sequences reveals strong secondary structure element conservation
AdoMet radical proteins - from structure to evolution - alignment of divergent protein sequences reveals strong secondary structure element conservation
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DOI：
10.1093/nar/gkh728
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发表时间：
2004-01-01
影响因子：
14.9
通讯作者：
Drennan, CL
中科院分区：
文献类型：
--
作者：
Nicolet, Y;Drennan, CL
在 AdoMet 自由基超家族的首次生物信息学研究中，已对 S-腺苷-L-甲硫氨酸 (AdoMet) 自由基蛋白的 18 个亚类进行了比对，以利用晶体学信息。最近解析的生物素合酶（BioB）的X射线结构用于指导多序列比对，并且最近解析的粪卟啉原III氧化酶（HemN）的X射线结构用作对照。尽管 BioB 和 HemN 之间的序列同一性较低，为 9%，但多重序列比对正确预测了 HemN 中除一个核心螺旋之外的所有螺旋，并正确预测了酶活性位点中的残基。这种排列进一步表明，AdoMet 自由基蛋白可能已从半桶结构 (alphabeta)(4) 进化为四分之三桶结构（(06 到全桶结构 (alphabeta)(8)）。它预测厌氧核糖核苷酸还原酶 (RNR) 激活酶（一种古老的酶，有人认为它是 RNA 和 DNA 世界之间的纽带）将具有半桶结构，而四分之三桶结构，以 HemN 为代表的，将是 AdoMet 自由基酶最常见的结构，并且该超家族中较少的成员将加入 BioB 使用完整的 (alphabeta)(8) TIM 桶折叠来进行自由基化学。桶结构的这些差异也解释了 AdoMet 自由基酶如何作用于大小范围从 10 个原子到 608 个残基蛋白质的底物。
Eighteen subclasses of S-adenosyl-L-methionine (AdoMet) radical proteins have been aligned in the first bioinformatics study of the AdoMet radical superfamily to utilize crystallographic information. The recently resolved X-ray structure of biotin synthase (BioB) was used to guide the multiple sequence alignment, and the recently resolved X-ray structure of coproporphyrinogen III oxidase (HemN) was used as the control. Despite the low 9% sequence identity between BioB and HemN, the multiple sequence alignment correctly predicted all but one of the core helices in HemN, and correctly predicted the residues in the enzyme active site. This alignment further suggests that the AdoMet radical proteins may have evolved from half-barrel structures (alphabeta)(4) to three-quarter-barrel structures ((06 to full-barrel structures (alphabeta)(8). It predicts that anaerobic ribonucleotide reductase (RNR) activase, an ancient enzyme that, it has been suggested, serves as a link between the RNA and DNA worlds, will have a half-barrel structure, whereas the three-quarter barrel, exemplified by HemN, will be the most common architecture for AdoMet radical enzymes, and fewer members of the superfamily will join BioB in using a complete (alphabeta)(8) TIM-barrel fold to perform radical chemistry. These differences in barrel architecture also explain how AdoMet radical enzymes can act on substrates that range in size from 10 atoms to 608 residue proteins.