Bioinformatic evidence for a widely distributed, ribosomally produced electron carrier precursor, its maturation proteins, and its nicotinoprotein redox partners.
Bioinformatic evidence for a widely distributed, ribosomally produced electron carrier precursor, its maturation proteins, and its nicotinoprotein redox partners.
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DOI：
10.1186/1471-2164-12-21
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发表时间：
2011-01-11
期刊：
影响因子：
4.4
通讯作者：
Haft DH
中科院分区：
文献类型：
--
作者：
Haft DH
自由基SAM（RSAM）结构域中的酶在各种生物学过程中使用，包括RNA修饰，酶激活，细菌素核心肽成熟和辅因子生物合成。进化压力和与其他细胞成分的关系对每类含RSAM的系统施加了可识别的语法，这是通过各种比较基因组学分析获得的结果的塑造模式。
在许多静脉细菌中发现的一个未表征的基因簇，并且在富有企业，氯反llexi，deltaproteobacteria和一个古细胞质粒中含有PQQQE样的RSAM蛋白家族，其中包括来自结核分枝杆菌的RV0693。成员出现在我们指定“霉菌素”的大小类似于细菌蛋白和pqqqa的大小相似，吡咯喹啉奎因酮（PQQ）的前体（PQQ）聚集了。基于这些标记物的分布的部分系统发育分析（PPP）确定了霉菌素簇，但也确定了第二层高分蛋白。令人惊讶的是，该层在三种无关类别的烟蛋白中，每个基因组中的每个基因组中最多有31个成员。该模式表明这些变体酶不仅需要NAD（P），还需要新型的基因簇。使用类似于PPP的工具Simbal进行了进一步的研究，以搜索这些烟蛋白，以了解多个基因组与霉菌肌动蛋白的存在最有关系的子序列。对于短链脱氢酶/还原酶（SDR）和含铁脱氢酶家族的，将Simbal的顶级得分序列与同源溶液溶液结构相提并论，显示了以NAD（P）结合位点而不是底物结合或活性位点残基上为中心的信号。先前对这些蛋白质中的某些蛋白质的研究表明，不可分割的NAD辅助因子，因此体外酶促活性需要人工电子受体，例如N，N-二甲基-4-硝基苯胺（NDMA）才能使酶循环。
综上所述，这些发现表明，霉菌素前体是由RV0693家族RSAM蛋白和其他酶的其他酶修饰的。它变成了电子载体分子，它像NDMA和其他人造电子受体一样在体内服务。来自三个不同烟蛋白家族的亚类显示与霉菌素的“仅”关系，因为它们需要其存在。该框架提出了一个隔离的氧化还原池，其中霉菌菌蛋白介导了酶与不合格的辅助因子之间的通信。
Enzymes in the radical SAM (rSAM) domain family serve in a wide variety of biological processes, including RNA modification, enzyme activation, bacteriocin core peptide maturation, and cofactor biosynthesis. Evolutionary pressures and relationships to other cellular constituents impose recognizable grammars on each class of rSAM-containing system, shaping patterns in results obtained through various comparative genomics analyses. An uncharacterized gene cluster found in many Actinobacteria and sporadically in Firmicutes, Chloroflexi, Deltaproteobacteria, and one Archaeal plasmid contains a PqqE-like rSAM protein family that includes Rv0693 from Mycobacterium tuberculosis. Members occur clustered with a strikingly well-conserved small polypeptide we designate "mycofactocin," similar in size to bacteriocins and PqqA, precursor of pyrroloquinoline quinone (PQQ). Partial Phylogenetic Profiling (PPP) based on the distribution of these markers identifies the mycofactocin cluster, but also a second tier of high-scoring proteins. This tier, strikingly, is filled with up to thirty-one members per genome from three variant subfamilies that occur, one each, in three unrelated classes of nicotinoproteins. The pattern suggests these variant enzymes require not only NAD(P), but also the novel gene cluster. Further study was conducted using SIMBAL, a PPP-like tool, to search these nicotinoproteins for subsequences best correlated across multiple genomes to the presence of mycofactocin. For both the short chain dehydrogenase/reductase (SDR) and iron-containing dehydrogenase families, aligning SIMBAL's top-scoring sequences to homologous solved crystal structures shows signals centered over NAD(P)-binding sites rather than over substrate-binding or active site residues. Previous studies on some of these proteins have revealed a non-exchangeable NAD cofactor, such that enzymatic activity in vitro requires an artificial electron acceptor such as N,N-dimethyl-4-nitrosoaniline (NDMA) for the enzyme to cycle. Taken together, these findings suggest that the mycofactocin precursor is modified by the Rv0693 family rSAM protein and other enzymes in its cluster. It becomes an electron carrier molecule that serves in vivo as NDMA and other artificial electron acceptors do in vitro. Subclasses from three different nicotinoprotein families show "only-if" relationships to mycofactocin because they require its presence. This framework suggests a segregated redox pool in which mycofactocin mediates communication among enzymes with non-exchangeable cofactors.
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DOI：
10.1007/bf00280008
发表时间：
1992-03-01
期刊：
MOLECULAR AND GENERAL GENETICS
影响因子：
--
作者：
MEULENBERG, JJM;SELLINK, E;POSTMA, PW
通讯作者：
POSTMA, PW
DOI：
10.1111/j.1432-1033.1997.00282.x
发表时间：
1997-09-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Norin, A;VanOphem, PW;Jornvall, H
通讯作者：
Jornvall, H
影响因子：
4.8
作者：
van der Werf, MJ;van der Ven, C;van Berkel, WJH
通讯作者：
van Berkel, WJH
影响因子：
14.9
作者：
Jensen LJ;Kuhn M;Stark M;Chaffron S;Creevey C;Muller J;Doerks T;Julien P;Roth A;Simonovic M;Bork P;von Mering C
通讯作者：
von Mering C
影响因子：
2.9
作者：
Kawulka, KE;Sprules, T;Vederas, JC
通讯作者：
Vederas, JC