Protein motifs .9. The nicotinamide dinucleotide binding motif: A comparison of nucleotide binding proteins
Protein motifs .9. The nicotinamide dinucleotide binding motif: A comparison of nucleotide binding proteins
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DOI：
10.1096/fasebj.10.11.8836039
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发表时间：
1996-09-01
期刊：
影响因子：
4.8
通讯作者：
Bellamacina, CR
中科院分区：
文献类型：
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作者：
Bellamacina, CR
经典的烟酰胺腺嘌呤二核苷酸（NAD（+））结合蛋白含有β α β α β单位。通过比较14种这样的蛋白质，观察到额外的β链与该单元结合形成“核心”拓扑结构，这是结合辅因子所需的最小结构。虽然烟酰胺结合蛋白的辅因子结合结构域的总体拓扑结构不同，但它们都至少包含核心拓扑结构。核心拓扑结构的前30-35个氨基酸，称为“指纹"区域，可诊断二核苷酸结合折叠的存在。该指纹区域有四个特征：1）磷酸盐结合共有序列，GXGXXG，2）通常由小疏水氨基酸占据的六个位置，3）保守的带负电荷的残基，（Glu或Asp），和4）保守的带正电荷的残基（Arg或Lys），经典烟酰胺结合蛋白的核心拓扑结构与主链原子的均方根偏差在0.7至4.7埃范围内很好地重叠。辅因子和蛋白质之间的保守相互作用（在研究的12种经典烟酰胺结合蛋白中的8种中发现）是NAD（P）（+）的焦磷酸氧与磷酸结合螺旋（β α β α β单位的第一个α螺旋）的羧基末端甘氨酸之间的氢键。经典的烟酰胺结合蛋白都在相同的位置和方向结合其辅因子，辅因子本身在每个结构中采用类似的延伸构象。虽然观察到的频率低于经典折叠，但许多非经典折叠模式也被结合NAD（P）（+）的蛋白质使用。
Classical nicotinamide adenine dinucleotide (NAD(+)) binding proteins contain a beta alpha beta alpha beta unit. By comparing 14 such proteins, it is observed that an additional beta strand associates with this unit to form the ''core'' topology, the minimum structure necessary to bind cofactor. Although the overall topologies of the cofactor binding domains of nicotinamide binding proteins vary, they all contain at least the core topology, The first 30-35 amino acids of the core topology, called the ''fingerprint'' region, are diagnostic for the presence of a dinucleotide binding fold, There are four characteristics of this fingerprint region: 1) a phosphate binding consensus sequence, GXGXXG, 2) six positions usually occupied by small hydrophobic amino acids, 3) a conserved, negatively charged residue (Glu or Asp) at the end of the second beta strand of the fingerprint region, and 4) a conserved positively charged residue (Arg or Lys) at the beginning of the first beta strand of the fingerprint region, The core topologies of the classical nicotinamide binding proteins overlap well with root mean squared deviations of main chain atoms ranging from 0.7 to 4.7 Angstrom. A conserved interaction (found in 8 of the 12 classical nicotinamide binding proteins studied) between the cofactor and the protein is a hydrogen bond between the pyrophosphate oxygen of NAD(P)(+) and the carboxy-terminal glycine of the phosphate binding helix, the first alpha helix of the beta alpha beta alpha beta unit. The classical nicotinamide binding proteins all bind their cofactor in the same location and orientation, with the cofactor itself adopting a similar extended conformation in every structure. Although observed less frequently than the classical fold, numerous nonclassical folding patterns are also used by proteins that bind NAD(P)(+).