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Review

Binding Pattern and Structural Interactome of the Anticancer Drug 5-Fluorouracil: A Critical Review

1
Department of Beauty Science, National Taichung University of Science and Technology, Taichung City 403, Taiwan
2
Department of Biomedical Sciences, Chung Shan Medical University, Taichung City 402, Taiwan
3
Department of Medical Research, Chung Shan Medical University Hospital, Taichung City 402, Taiwan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(6), 3404; https://doi.org/10.3390/ijms25063404
Submission received: 5 February 2024 / Revised: 13 March 2024 / Accepted: 15 March 2024 / Published: 17 March 2024
(This article belongs to the Special Issue Natural Products and Synthetic Compounds for Drug Development)

Abstract

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.
Keywords: 5-fluorouracil; interactome; anticancer; binding mode; crystal structure; SSB; dihydroorotase; dihydropyrimidinase; PISA; PLIP 5-fluorouracil; interactome; anticancer; binding mode; crystal structure; SSB; dihydroorotase; dihydropyrimidinase; PISA; PLIP

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MDPI and ACS Style

Lin, E.-S.; Huang, C.-Y. Binding Pattern and Structural Interactome of the Anticancer Drug 5-Fluorouracil: A Critical Review. Int. J. Mol. Sci. 2024, 25, 3404. https://doi.org/10.3390/ijms25063404

AMA Style

Lin E-S, Huang C-Y. Binding Pattern and Structural Interactome of the Anticancer Drug 5-Fluorouracil: A Critical Review. International Journal of Molecular Sciences. 2024; 25(6):3404. https://doi.org/10.3390/ijms25063404

Chicago/Turabian Style

Lin, En-Shyh, and Cheng-Yang Huang. 2024. "Binding Pattern and Structural Interactome of the Anticancer Drug 5-Fluorouracil: A Critical Review" International Journal of Molecular Sciences 25, no. 6: 3404. https://doi.org/10.3390/ijms25063404

APA Style

Lin, E.-S., & Huang, C.-Y. (2024). Binding Pattern and Structural Interactome of the Anticancer Drug 5-Fluorouracil: A Critical Review. International Journal of Molecular Sciences, 25(6), 3404. https://doi.org/10.3390/ijms25063404

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