Superfamily active site templates
Superfamily active site templates
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DOI：
10.1002/prot.20099
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发表时间：
2004-06-01
影响因子：
2.9
通讯作者：
Babbitt, PC
中科院分区：
文献类型：
--
作者：
Meng, EC;Polacco, BJ;Babbitt, PC
我们表明，只有几个功能上重要的残基组成的三维签名可以诊断的超家族的酶的成员。使用烯醇化酶超家族作为模型系统，我们证明，这样的签名，或模板，可以识别超家族成员的结构数据库中具有高灵敏度和特异性。这是值得注意的，因为超家族可以是高度多样化的，成员催化许多不同的整体反应;统一的原则可以是保守的部分反应或化学能力。因此，我们对超家族的定义取决于参与保守功能的残基的配置，而不仅仅是折叠相似性。基于这种活性位点模板而不是折叠相似性的结构搜索的一个明显优势是特异性，具有不同功能特征的超家族可以在具有相同折叠的大量蛋白质中鉴定，例如（β/α）（8）桶。初步结果提出了一个额外的一组酶与不同的倍，卤酸脱卤酶超家族，这表明这种方法可能是一般有用的分配阅读框架的未知功能，以特定的超家族，从而允许推断他们的一些功能特性。(C)2004 Wiley-Liss，Inc.
We show that three-dimensional signatures consisting of only a few functionally important residues can be diagnostic of membership in superfamilies of enzymes. Using the enolase superfamily as a model system, we demonstrate that such a signature, or template, can identify superfamily members in structural databases with high sensitivity and specificity. This is remarkable because superfamilies can be highly diverse, with members catalyzing many different overall reactions; the unifying principle can be a conserved partial reaction or chemical capability. Our definition of a superfamily thus hinges on the disposition of residues involved in a conserved function, rather than on fold similarity alone. A clear advantage of basing structure searches on such active site templates rather than on fold similarity is the specificity with which superfamilies with distinct functional characteristics can be identified within a large set of proteins with the same fold, such as the (beta/alpha)(8) barrels. Preliminary results are presented for an additional group of enzymes with a different fold, the haloacid dehalogenase superfamily, suggesting that this approach may be generally useful for assigning reading frames of unknown function to specific superfamilies and thereby allowing inference of some of their functional properties. (C) 2004 Wiley-Liss, Inc.