Shaw Eudean, McCue Lee Ann, Lawrence Charles E, Dordick Jonathan S
Department of Chemical Engineering, Rensselaer Polytechnic Institute, Troy, New York, USA.
Proteins. 2002 May 1;47(2):163-8. doi: 10.1002/prot.10083.
The alpha/beta hydrolases constitute a large protein superfamily that mainly consists of enzymes that catalyze a diverse range of reactions. These proteins exhibit the alpha/beta hydrolase fold, the essential features of which have recently been delineated: the presence of at least five parallel beta-strands, a catalytic triad in a specific order (nucleophile-acid-histidine), and a nucleophilic elbow. Because of the difficulties experimentally in identifying protein structures, we have used a Bayesian computational algorithm (PROBE) to identify the members of this superfamily based on distant sequence relationships. We found that the presence of five sequence motifs, which contain residues important for substrate binding and stabilization of the fold, are required for membership in this superfamily. The superfamily consists of at least 909 members, including the N-myc downstream regulated proteins, which are believed to be involved in cell differentiation. Unlike most of the other superfamily members, the N-myc downstream regulated proteins have never been proposed to possess the alpha/beta hydrolase fold and do not appear to be hydrolases.
α/β水解酶构成了一个庞大的蛋白质超家族,主要由催化各种反应的酶组成。这些蛋白质呈现出α/β水解酶折叠结构,其基本特征最近已被阐明:至少存在五条平行的β链、特定顺序的催化三联体(亲核体-酸-组氨酸)以及一个亲核肘部。由于在实验上鉴定蛋白质结构存在困难,我们使用了一种贝叶斯计算算法(PROBE),基于远缘序列关系来鉴定这个超家族的成员。我们发现,该超家族的成员需要存在五个序列基序,这些基序包含对底物结合和折叠结构稳定很重要的残基。这个超家族至少由909个成员组成,包括N- myc下游调控蛋白,据信这些蛋白参与细胞分化。与大多数其他超家族成员不同,N- myc下游调控蛋白从未被认为具有α/β水解酶折叠结构,似乎也不是水解酶。