STRUCTURAL CONSEQUENCES OF SEQUENCE PATTERNS IN THE FINGERPRINT REGION OF THE NUCLEOTIDE BINDING FOLD - IMPLICATIONS FOR NUCLEOTIDE SPECIFICITY
STRUCTURAL CONSEQUENCES OF SEQUENCE PATTERNS IN THE FINGERPRINT REGION OF THE NUCLEOTIDE BINDING FOLD - IMPLICATIONS FOR NUCLEOTIDE SPECIFICITY
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DOI：
10.1016/0022-2836(92)90848-e
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发表时间：
1992-11-20
影响因子：
5.6
通讯作者：
STILLMAN, TJ
中科院分区：
文献类型：
--
作者：
BAKER, PJ;BRITTON, KL;STILLMAN, TJ
本文分析了7种不同酶晶体结构中二核苷酸结合βαβ基序的三维结构和一级序列。我们已经确定了腺嘌呤核糖与含有指纹序列GXGXXG/A的富含甘氨酸的旋体的氢键以直接或间接的机制发生，这取决于指纹序列的性质，但与辅酶特异性无关。相互作用类型的主要决定因素是占据上述指纹最后位置的残留物的性质。在NAD+连接的脱氢酶中，酸性残基通常用于与腺嘌呤核糖羟基形成重要的氢键，迄今为止，该残基被认为是NAD+特异性的一个指标。然而，基于共生梭菌的NAD+连接谷氨酸脱氢酶（GDH）的三维结构已经证明该残基不是构建NAD+结合位点的普遍要求。此外，考虑到序列同源性，明确地确定了NADP+和双特异性谷氨酸脱氢酶中等效的酸性残基。这个残基在这些酶中的保守性，加上它与2 '磷酸的接近，这意味着它在三维结构上与c有必要的相似性。symbiosumGDH，暗示该残基通过水介导或直接氢键方案识别2 '磷酸。对后者的分析使我们认为NADP+结合酶对2 ‘磷酸基团的识别可能存在两种模式，这两种模式是由2 ’磷酸的电离状态来区分的。
The dinucleotide binding βαβ motif in the crystal structures of seven different enzymes has been analysed in terms of their three-dimensional structures and primary sequences. We have identified that the hydrogen bonding of the adenine ribose to the glycine-rich turn containing the fingerprint sequence GXGXXG/A occursviaa direct or indirect mechanism, depending on the nature of the fingerprint sequence but independent of coenzyme specificity. The major determinant of the type of interaction is the nature of the residue occupying the last position of the above fingerprint. In the NAD+-linked dehydrogenases, an acidic residue is commonly used to form important hydrogen bonds to the adenine ribose hydroxyls and, hitherto, this residue has been thought to be an indicator of NAD+specificity. However, on the basis of the three-dimensional structure of the NAD+-linked glutamate dehydrogenase (GDH) fromClostridium symbiosumwe have demonstrated that this residue is not a universal requirement for the construction of an NAD+binding site. Furthermore, considerations of sequence homology unambiguously identify an equivalent acidic residue in both NADP+and dual specificity glutamate dehydrogenases. The conservation of this residue in these enzymes, coupled to its close proximity to the 2′ phosphate implied by the necessary similarity in three-dimensional structure toC. symbiosumGDH, implicates this residue in the recognition of the 2′ phosphate eitherviawater-mediated or direct hydrogen-bonding schemes. Analysis of the latter has led us to suggest that two patterns of recognition for the 2′ phosphate group of NADP+-binding enzymes may exist, which are distinguished by the ionization state of the 2′ phosphate.