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THE CATALYTIC MECHANISM AND STRUCTURE OF THYMIDYLATE SYNTHASE
Abstract
Thymidylate synthase (TS, EC 2.1.1.45) catalyzes the reductive methylation of dUMP by CH2H4folate to produce dTMP and H2folate. Knowledge of the catalytic mechanism and structure of TS has increased substantially over recent years. Major advances were derived from crystal structures of TS bound to various ligands, the ability to overexpress TS in heterologous hosts, and the numerous mutants that have been prepared and analyzed. These advances, coupled with previous knowledge, have culminated in an in-depth understanding of many important molecular details of the reaction. We review aspects of TS catalysis that are most pertinent to understanding the current status of the structure and catalytic mechanism of the enzyme. Included is a discussion of available sources and assays for TS, a description of the enzyme's chemical mechanism and crystal structure, and a summary of data obtained from mutagenesis experiments.
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Cited by
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Erlanson, D. A., Braisted, A. C., Raphael, D. R., Randal, M., Stroud, R. M., Gordon, E. M., & Wells, J. A. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.17.9367 · Cited by 466
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Metadata
- Authors
- Carreras, C. W., & Santi, D. V.
- Venue
- Annual Review of Biochemistry
- Publisher
- Annual Reviews
- Published
- 1995-06
- Volume
- 64
- Issue
- 1
- Pages
- 721-762
- ISSN
- 0066-4154 (ISSN-L)
- 1545-4509
- OpenAlex
- W2176123637
- Cited by
- 768
- References
- 0
- FWCI
- 7.11
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: THE CATALYTIC MECHANISM AND STRUCTURE OF THYMIDYLATE SYNTHASE. https://app.cochat.ai/papers/10.1146/annurev.bi.64.070195.003445
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- Carreras, C. W., & Santi, D. V. (1995). THE CATALYTIC MECHANISM AND STRUCTURE OF THYMIDYLATE SYNTHASE. Annual Review of Biochemistry. https://doi.org/10.1146/annurev.bi.64.070195.003445
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