Champoux J J
Department of Microbiology School of Medicine, University of Washington, Seattle 98195, USA.
Prog Nucleic Acid Res Mol Biol. 1998;60:111-32. doi: 10.1016/s0079-6603(08)60891-0.
Human topoisomerase I can be divided into four domains based on homology alignments, physical properties, sensitivity to limited proteolysis, and fragment complementation studies. Roughly the first 197 amino acids represent the N-terminal domain that appears to be devoid of secondary structure and is likely important for targeting the enzyme to its sites of action within the nucleus of the cell. The core domain encompasses residues approximately 198 to approximately 651, is involved in catalysis, and is important for the preferential binding of the enzyme to supercoiled DNA. The C-terminal domain extends from residue approximately 697 to the end of the protein at residue 765 and contains the catalytically important active site tyrosine at position 723. The core and C-terminal domains are connected by a poorly conserved, protease-sensitive linker domain (residues approximately 652 to approximately 696) that has been implicated in DNA binding and may influence how long the enzyme remains in the nicked stated. Mutations that confer resistance to the topoisomerase I poison camptothecin are located in the core and C-terminal domains and presumably identify residues important for drug binding.
基于同源性比对、物理性质、对有限蛋白酶解的敏感性以及片段互补研究，人类拓扑异构酶I可分为四个结构域。大致前197个氨基酸代表N端结构域，该结构域似乎缺乏二级结构，可能对于将该酶靶向细胞内细胞核中的作用位点很重要。核心结构域包含大约198至大约651位的残基，参与催化作用，并且对于该酶与超螺旋DNA的优先结合很重要。C端结构域从大约697位残基延伸至蛋白质末端的765位残基，并在723位含有催化重要的活性位点酪氨酸。核心结构域和C端结构域由一个保守性较差、对蛋白酶敏感的连接结构域（大约652至大约696位残基）连接，该结构域与DNA结合有关，可能会影响该酶在切口状态下保持的时间。赋予对拓扑异构酶I毒药喜树碱抗性的突变位于核心结构域和C端结构域，大概确定了对药物结合重要的残基。
