STRUCTURE OF A PEPTIDE INHIBITOR BOUND TO THE CATALYTIC SUBUNIT OF CYCLIC ADENOSINE-MONOPHOSPHATE DEPENDENT PROTEIN-KINASE
STRUCTURE OF A PEPTIDE INHIBITOR BOUND TO THE CATALYTIC SUBUNIT OF CYCLIC ADENOSINE-MONOPHOSPHATE DEPENDENT PROTEIN-KINASE
复制标题
DOI：
10.1126/science.1862343
复制
发表时间：
1991-07-26
期刊：
影响因子：
56.9
通讯作者：
SOWADSKI, JM
中科院分区：
文献类型：
--
作者：
KNIGHTON, DR;ZHENG, JH;SOWADSKI, JM
20个氨基酸的肽抑制剂结合到环AMP依赖性蛋白激酶的催化亚基的结构，及其与酶的相互作用，进行了描述。配合物的X射线晶体结构是分析的基础。该肽抑制剂衍生自天然存在的热稳定蛋白激酶抑制剂，含有一个两亲性螺旋，随后是一个转角和一个延伸构象。延伸区域占据酶的两个叶之间的裂缝，并包含一个五个残基的共识识别序列共同的所有底物和肽抑制剂的催化亚基。肽的螺旋部分与疏水沟结合并传递高亲和力结合。来自两个结构域的环会聚在活性位点，并在三磷酸腺苷镁结合和催化位点处形成保守残基网络。与肽识别相关的非保守氨基酸在大的表面积上延伸。
The structure of a 20-amino acid peptide inhibitor bound to the catalytic subunit of cyclic AMP-dependent protein kinase, and its interactions with the enzyme, are described. The x-ray crystal structure of the complex is the basis of the analysis. The peptide inhibitor, derived from a naturally occurring heat-stable protein kinase inhibitor, contains an amphipathic helix that is followed by a turn and an extended conformation. The extended region occupies the cleft between the two lobes of the enzyme and contains a five-residue consensus recognition sequence common to all substrates and peptide inhibitors of the catalytic subunit. The helical portion of the peptide binds to a hydrophobic groove and conveys high affinity binding. Loops from both domains converge at the active site and contribute to a network of conserved residues at the sites of magnesium adenosine triphosphate binding and catalysis. Amino acids associated with peptide recognition, nonconserved, extend over a large surface area.