EVOLUTION OF ALCOHOL & ALDEHYDE DEHYDROGENASES

我的小组一直在使用配置文件服务器开发一个非常 醛脱氢酶的大的多重比对。 对准 现在包含超过120个序列，包括一些边缘蛋白质， 催化功能如透镜晶体蛋白。 特别是在寻找 与配置文件服务器关系最远的序列 无价之宝 我们也在寻找例子， 其他可能含有类似NAD结合位点的家族， 截短的比对，以提高找到这样的结构域的机会。 (It现在已知ALDH具有非传统的Rossmann折叠）。 否则，一个涉及对齐多个数据库的副项目也会 使用Profile Server。 这两个项目都是手稿， 准备. 我们在那个项目中所做的是反驳一个假设 基于将单个ADH和ALDH序列与 大约是这两个加起来的长度，都来自曲霉菌。 对眼睛 不熟悉ADH和ALDH的特征，假设 不是太不合理，但以前的Au没有意识到 （因为他们从来没有读过任何相关的文献！）就是没有一个 它们的配对残基是那些典型的保守的， 两个家庭。 我们做的是根据16个 ALDHs和大约100个ADH，并将侧写与大的 曲霉菌序列。 结果基本上说没有相似之处，但是 如果这个大蛋白确实代表了2的祖先融合， 它们以与先前提议相反的顺序融合， 驳斥了之前的假设， 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!