CRYSTAL-STRUCTURE OF THE CATALYTIC SUBUNIT OF CYCLIC ADENOSINE-MONOPHOSPHATE DEPENDENT PROTEIN-KINASE
CRYSTAL-STRUCTURE OF THE CATALYTIC SUBUNIT OF CYCLIC ADENOSINE-MONOPHOSPHATE DEPENDENT PROTEIN-KINASE
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DOI：
10.1126/science.1862342
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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
与20个氨基酸的底物类似物抑制剂复合的环腺苷一磷酸依赖性蛋白激酶的催化亚基的晶体结构已被解决，并在2.7埃分辨率下部分精制到R因子为0.212。采用差分傅立叶合成法定位三磷酸腺苷镁（MgATP）结合位点。酶的结构是双叶的，叶之间有一个很深的裂缝。裂缝由MgATP和一部分抑制肽填充。较小的叶主要由氨基末端序列组成，与核苷酸结合相关，其基本上反平行的β折叠结构构成了一种不寻常的核苷酸结合基序。较大的叶由螺旋结构主导，在畴界面处具有单个β-片层。该叶主要参与肽结合和催化。残基40至280构成了由100多种蛋白激酶共享的保守催化核心。这个保守的催化核心中的大多数不变氨基酸聚集在核苷酸结合和催化的位点。
The crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase complexed with a 20-amino acid substrate analog inhibitor has been solved and partially refined at 2.7 angstrom resolution to an R factor of 0.212. The magnesium adenosine triphosphate (MgATP) binding site was located by difference Fourier synthesis. The enzyme structure is bilobal with a deep cleft between the lobes. The cleft is filled by MgATP and a portion of the inhibitor peptide. The smaller lobe, consisting mostly of amino-terminal sequence, is associated with nucleotide binding, and its largely antiparallel beta-sheet architecture constitutes an unusual nucleotide binding motif. The larger lobe is dominated by helical structure with a single beta-sheet at the domain interface. This lobe is primarily involved in peptide binding and catalysis. Residues 40 through 280 constitute a conserved catalytic core that is shared by more than 100 protein kinases. Most of the invariant amino acids in this conserved catalytic core are clustered at the sites of nucleotide binding and catalysis.