Structural and functional analysis of the mitotic rotamase Pin1 suggests substrate recognition is phosphorylation dependent
Structural and functional analysis of the mitotic rotamase Pin1 suggests substrate recognition is phosphorylation dependent
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DOI：
10.1016/s0092-8674(00)80273-1
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发表时间：
1997-06-13
期刊：
影响因子：
64.5
通讯作者：
Noel, JP
中科院分区：
文献类型：
--
作者：
Ranganathan, R;Lu, KP;Noel, JP
人旋转异构酶或肽基脯氨酰顺反异构酶Pin 1是真核细胞周期G2/M转换所必需的保守的有丝分裂调节因子。我们报告的1.35埃晶体结构的Pin 1与AlaPro二肽和Pin 1的功能特性的初步表征。活性位点半胱氨酸的晶体结构以及pH滴定研究和诱变表明了一种催化机制，包括一般的酸碱和共价催化过程中的肽键异构化。Pin 1显示出对异构化脯氨酸键N-末端的酸性残基的偏好，这是由于该酸性侧链与碱性簇的相互作用。这提高了细胞周期调控中磷酸化介导的Pin 1-底物相互作用控制的可能性。
The human rotamase or peptidyl-prolyl cis-trans isomerase Pin1 is a conserved mitotic regulator essential for the G2/M transition of the eukaryotic cell cycle. We report the 1.35 Angstrom crystal structure of Pin1 complexed with an AlaPro dipeptide and the initial characterization of Pin1's functional properties. The crystallographic structure as well as pH titration studies and mutagenesis of an active site cysteine suggest a catalytic mechanism that includes general acid-base and covalent catalysis during peptide bond isomerization. Pin1 displays a preference for an acidic residue N-terminal to the isomerized proline bond due to interaction of this acidic side chain with a basic cluster. This raises the possibility of phosphorylation-mediated control of Pin1-substrate interactions in cell cycle regulation.