EVOLUTION OF ALCOHOL & ALDEHYDE DEHYDROGENASES

我的团队一直在使用配置文件服务器来开发非常 乙醛脱氢酶的大的多重排列。路线 现在包含超过120个序列，包括一些边缘蛋白 晶状体蛋白等催化功能。尤其是在寻找 配置文件服务器中关联最远的序列是 无价之宝。我们还在寻找以下方面的例子 其他可能包含类似NAD结合位点的家族，通过使用 截断的比对，以增加找到这些结构域的机会。 (现在已知ALDH有非传统的Rossmann褶皱)。 否则，涉及精氨酸酶比对的副项目也有 利用了配置文件服务器。这两个项目都是 准备工作。我们在那个项目中所做的是驳斥一个假说 基于将单个ADH和ALDH序列与 大约2个加在一起的长度，都是来自曲霉。直达眼睛 由于不熟悉ADHS和ALDHs的特点，假设 并不是太不合理，但以前的非盟没有意识到的是 (因为他们从来没有读过任何相关的文献！)是不是没有一个 它们的匹配残基是典型的保守的 2个家庭。我们所做的是根据16个家庭运行每个家庭的档案 ALDH和大约100个ADH，并对大的 曲霉菌序列。结果基本上说没有相似之处，但 如果这个大的蛋白质确实代表了2的祖先融合， 它们以与先前提案相反的顺序融合在一起，因此 驳斥了早先关于一个不错的、公正的、统计的假设 基础！

My group has been using the profile server in developing a very large multiple alignment of aldehyde dehydrogenases. The alignment now contains over 120 sequences, including some proteins of marginal catalytic function such as lens crystallins. Particularly in finding the most distantly related sequences the Profile server has been invaluable. We are also in the process of searching for examples from other families that might contain a similar NAD-binding site, by using truncated alignments to enhance the chances of finding such domains. (It is now known that ALDHs have non-traditional Rossmann folds). Otherwise, a side project involving an alignment of arginases also has made use of the Profile server. Both projects are manuscripts in preparation. What we did in that project was refute a hypothesis based on aligning single ADH and ALDH sequences with a protein of about the length of the 2 combined, all from Aspergillus. To eyes unfamiliar with the characteristics of ADHs and ALDHs, the hypothesis was not too unreasonable, but what previous au's failed to appreciate (since they never read any relevant literature!) was that none of their matching residues were among those typically conserved in those 2 families. What we did was run profiles of each family based on 16 ALDHs and about 100 ADHs, and run the profile against the big Aspergillus sequence. The result basically said no similarity, but that if the big protein did represent an ancestral fusion of the 2, they were fused in opposite order from the earlier proposal, thereby refuting the whole earlier hypothesis on a nice impartial, statistical basis!