Dr Rafael Guimaraes da Silva
Senior Lecturer
Research areas
Enzymes catalyse virtually all chemical reactions in living organisms, making their rates compatible with life. These proteins (and sometimes RNAs) have evolved to utilize a range of strategies to achieve incredible rate enhancements in comparison with the corresponding non-catalysed reactions. The study of enzymatic mechanisms is fundamental to elucidate how enzymes work in physical and chemical terms, to guide the rational design of inhibitors, and to help engineer new activities. Here we apply techniques of biochemistry and physical organic chemistry to unravel the mechanisms of enzymatic reactions catalysed by bacterial enzymes important for pathogenic bacteria to survive and thrive, and by human enzymes important for cancer cells to survive and spread. Particular emphasis is given to transition-state structure and to the role of protein dynamics in energy barrier crossing.
PhD supervision
- Lily Bates
- Soumili Biswas
- Anna Carberry
- Myriam Kabu
- Ennio Pecaver
Selected publications
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Open access
Improved nucleoside (2'-deoxy)ribosyltransferases maximize enzyme promiscuity while maintaining catalytic efficiency
Tang, P., Zickuhr, G. M., Dickson, A. L., Harding, C. J., Devi, S., Lebl, T., Harrison, D. J., da Silva, R. G. & Melo Czekster, C., 21 Nov 2025, In: ACS Chemical Biology. 20, 11, p. 2547–2553 7 p.Research output: Contribution to journal › Letter › peer-review
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Open access
Kinetic and thermodynamic characterization of human 4-oxo-L-proline reductase catalysis
Pecaver, E., Zickuhr, G. M., Machado, T. F. G., Harrison, D. J. & da Silva, R. G., 18 Feb 2025, In: Biochemistry. 64, 4, p. 860-870 11 p.Research output: Contribution to journal › Article › peer-review
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Open access
The energy landscape of N-ribosidic bond cleavage catalysed by 2′-deoxynucleoside 5′-phosphate N-hydrolase 1
Carberry, A. E., Das, T., Harrison, D., Hirschi, J. & da Silva, R. G., 12 Dec 2025, In: Biochemical Journal. 482, 24, p. 1-22 BCJ20253400.Research output: Contribution to journal › Article › peer-review
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Open access
Allosteric activation unveils protein-mass modulation of ATP phosphoribosyltransferase product release
Read, B., Mitchell, J. B. O. & da Silva, R. G., 6 Apr 2024, In: Communications Chemistry. 7, 13 p., 77.Research output: Contribution to journal › Article › peer-review
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Open access
Crystal structure, steady-state and pre-steady-state kinetics of Acinetobacter baumannii ATP phosphoribosyltransferase
Read, B., Cadzow, A., Alphey, M. S., Mitchell, J. B. O. & da Silva, R. G., 16 Jan 2024, In: Biochemistry. 63, 2, p. 230-240 11 p.Research output: Contribution to journal › Article › peer-review
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Open access
Human 2'-deoxynucleoside 5'-phosphate N-hydrolase 1: the catalytic roles of Tyr24 and Asp80
Carberry, A. E., Devi, S., Harrison, D. J. & da Silva, R. G., 2 Apr 2024, In: ChemBioChem. 25, 7, 10 p., e202400047.Research output: Contribution to journal › Article › peer-review
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Open access
Snapshots of the reaction coordinate of a thermophilic 2'-deoxyribonucleoside/ribonucleoside transferase
Tang, P., Harding, C. J., Dickson, A., da Silva, R. G., Harrison, D. J. & Melo Czekster, C., 1 Mar 2024, In: ACS Catalysis. 14, 5, p. 3090-3102 13 p.Research output: Contribution to journal › Article › peer-review
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Open access
Catalytic cycle of the bifunctional enzyme phosphoribosyl-ATP pyrophosphohydrolase/phosphoribosyl-AMP cyclohydrolase
Fisher, G., Pecaver, E., Read, B., Leese, S., Laing, E., Dickson, A., Melo Czekster, C. & da Silva, R. G., 2 Jun 2023, In: ACS Catalysis. 13, 11, p. 7669-7679 11 p.Research output: Contribution to journal › Article › peer-review
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Employing deuterium kinetic isotope effects to uncover the mechanism of (R)-3-hydroxybutyrate dehydrogenase
Machado, T. F. G. & da Silva, R. G., 5 Apr 2023, New experimental probes for enzyme specificity and mechanism. Richard, J. P. & Moran, G. (eds.). Amsterdam: Academic Press/Elsevier , p. 225-240 16 p. (Methods in enzymology; vol. 685).Research output: Chapter in Book/Report/Conference proceeding › Chapter
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Open access
Human 2'-deoxynucleoside 5'-phosphate N-hydrolase 1: mechanism of 2'-deoxyuridine 5'-monophosphate hydrolysis
Devi, S., Carberry, A. E., Zickuhr, G. M., Dickson, A., Harrison, D. J. & da Silva, R. G., 5 Sept 2023, In: Biochemistry. 62, 17, p. 2658-2668 11 p.Research output: Contribution to journal › Article › peer-review