5-氟尿嘧啶(5-FU)是最广泛使用的化疗药物之一。尽管经过了60多年的研究,缺乏关于5-FU如何与蛋白质结合的系统概述。研究5-FU与蛋白质的特异性结合模式对于识别其他相互作用的蛋白质和理解其医学意义至关重要。在这次审查中,基于可用的复杂结构进行5-FU结合环境的分析。从2001年最早的复杂结构到现在,5-FU结合后出现两组残基,分类为P型和R型残基。这些具有5-FU的高频相互作用残基包括带正电荷的残基Arg和Lys(P型)和环残基Phe,Tyr,Trp,和他的(R型)。由于它们的高发生率,5-FU结合模式被简单地分为三种类型,基于具有5-FU:1型(P-R型)的相互作用残基(<4加之),2型(P型),和类型3(R型)。总之,在14个选定的复杂结构中,8符合类型1,2符合类型2,4符合类型3。还检查了涉及5-FU的N1,N3,O4和F5原子的高相互作用频率的残基。总的来说,这些相互作用分析为蛋白质口袋内5-FU的特异性结合模式提供了结构视角,并有助于构建描述抗癌药物5-FU相关性的结构相互作用组.
5-Fluorouracil (5-FU) stands as one of the most widely prescribed chemotherapeutics. Despite over 60 years of study, a systematic synopsis of how 5-FU binds to proteins has been lacking. Investigating the specific binding patterns of 5-FU to proteins is essential for identifying additional interacting proteins and comprehending their medical implications. In this
review, an analysis of the 5-FU binding environment was conducted based on available complex structures. From the earliest complex structure in 2001 to the present, two groups of residues emerged upon 5-FU binding, classified as P- and R-type residues. These high-frequency interactive residues with 5-FU include positively charged residues Arg and Lys (P type) and ring residues Phe, Tyr, Trp, and His (R type). Due to their high occurrence, 5-FU binding modes were simplistically classified into three types, based on interactive residues (within <4 Å) with 5-FU: Type 1 (P-R type), Type 2 (P type), and Type 3 (R type). In summary, among 14 selected complex structures, 8 conform to Type 1, 2 conform to Type 2, and 4 conform to Type 3. Residues with high interaction frequencies involving the N1, N3, O4, and F5 atoms of 5-FU were also examined. Collectively, these interaction analyses offer a structural perspective on the specific binding patterns of 5-FU within protein pockets and contribute to the construction of a structural
interactome delineating the associations of the anticancer drug 5-FU.