人胸苷酸合成酶界面残基的丙氨酸突变体解析了变构抗癌肽结合模式的关键特征。
Alanine mutants of the interface residues of human thymidylate synthase decode key features of the binding mode of allosteric anticancer peptides.
作者信息
Tochowicz Anna, Santucci Matteo, Saxena Puneet, Guaitoli Giambattista, Trande Matteo, Finer-Moore Janet, Stroud Robert M, Costi Maria P
机构信息
Department of Biochemistry and Biophysics, University of California-San Francisco , 600 16th Street, San Francisco, California 94158, United States.
出版信息
J Med Chem. 2015 Jan 22;58(2):1012-8. doi: 10.1021/jm5011176. Epub 2014 Dec 29.
Abstract
Allosteric peptide inhibitors of thymidylate synthase (hTS) bind to the dimer interface and stabilize the inactive form of the protein. Four interface residues were mutated to alanine, and interaction studies were employed to decode the key role of these residues in the peptide molecular recognition. This led to the identification of three crucial interface residues F59, L198, and Y202 that impart activity to the peptide inhibitors and suggest the binding area for further inhibitor design.
摘要
胸苷酸合成酶（hTS）的变构肽抑制剂与二聚体界面结合并稳定蛋白质的无活性形式。四个界面残基被突变为丙氨酸，并采用相互作用研究来解读这些残基在肽分子识别中的关键作用。这导致鉴定出三个关键的界面残基F59、L198和Y202，它们赋予肽抑制剂活性，并为进一步的抑制剂设计指明了结合区域。
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