Human cytidine deaminase: A three-dimensional homology model of a tetrameric metallo-enzyme inferred from the crystal structure of a distantly related dimeric homologue
Human cytidine deaminase: A three-dimensional homology model of a tetrameric metallo-enzyme inferred from the crystal structure of a distantly related dimeric homologue
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DOI：
10.1016/j.jmgm.2005.10.008
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发表时间：
2006-09-01
影响因子：
2.9
通讯作者：
Vita, Alberto
中科院分区：
文献类型：
--
作者：
Costanzi, Stefano;Vincenzetti, Silvia;Vita, Alberto
胞苷脱氨酶(CDA)是一种胞质金属蛋白，根据物种的不同，其功能单位可以是同源四聚体(T-CDA)或同源二聚体(DCDA)。1994年，首次报道了二聚体大肠杆菌CDA的晶体结构。然而，直到2002年才确定了四聚体CDA的晶体结构。在揭示四聚体CDA的实验结构之前，我们以二聚体大肠杆菌CDA的晶体结构为模板，推导了人T-CDA的同源模型。将我们的理论模型与2004年发表的人T-CDA的晶体结构进行了比较，验证了我们的预测：在我们的模型中，不仅可以高精度地确定单体的结构特征和结合位置的细节，而且还可以确定亚基的多聚体排列。通过对不同生物的CDA进行系统发育分析，我们证明了E.ColiCDA是人类酶最远已知的同源物之一。然而，尽管进化距离很远，更重要的是，它们的功能单位有不同的多聚体排列，但事实证明，大肠杆菌CDA拥有所有必要的信息，可以准确地推断其人类同源物的结构。(C)2005 Elsevier Inc.保留所有权利。
Cytidine deaminase (CDA) is a cytosolic metalloprotein whose functional unit can be either a homotetramer (T-CDA) or a homodimer (DCDA), depending on the species. In 1994, the first crystal structure of the dimeric Escherichia coli CDA has been published. However, a crystal structure of a tetrameric CDA was not determined until 2002. Prior to the disclosure of the experimentally elucidated structure of a tetrameric CDA, we derived a homology model of the-human T-CDA employing the crystal structure of the dimeric E. coli CDA as a template. The comparison of our theoretical model with the crystal structure of the human T-CDA, subsequently published in 2004, validates our prediction: not only of the structural features of the monomer and the details of the binding site, but also the multimeric arrangement of the subunits were determined with high accuracy in our model. By means of a phylogenetic analysis conducted on CDAs from various organisms, we demonstrate that the E. coli CDA is one of the furthest known homologues of the human enzyme. Nonetheless, despite the evolutionary distance and, more importantly, the different multimeric arrangement of their functional units, the E. coli CDA proved to have all the necessary information to accurately infer the structure of its human homologue. (c) 2005 Elsevier Inc. All rights reserved.