Dr Rafael Guimaraes da Silva

Senior Lecturer

Phone: +44 (0)1334 46 3496
Email: rgds@st-andrews.ac.uk

Teaching

BL2104, BL3310

Research areas

Enzymes catalyse virtually all chemical reactions in living organisms, making their rates compatible with life. These proteins, and sometimes RNA’s, 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 chemistry to unravel the mechanisms of enzymatic reactions involved in bacterial histidine and 5-aminolevulinic acid biosynthesis and in human protein histidine phosphorylation. Particular emphasis is given to transition-state structure and to the role of protein dynamics in energy barrier crossing.

PhD supervision

Anna Carberry
Ennio Pecaver
Myriam Kabu

Selected publications

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
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
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
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
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
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
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
Open access

Allosteric inhibition of Acinetobacter baumannii ATP phosphoribosyltransferase by protein:dipeptide and protein:protein Interactions
Read, B. J., Fisher, G., Wissett, O. L. R., Machado, T. F. G., Nicholson, J., Mitchell, J. B. O. & da Silva, R. G., 14 Jan 2022, In: ACS Infectious Diseases. 8, 1, p. 197-209 13 p.
Research output: Contribution to journal › Article › peer-review
Open access

Allosteric rescue of catalytically impaired ATP phosphoribosyltransferase variants links protein dynamics to active-site electrostatic preorganisation
Fisher, G., Corbella, M., Alphey, M. S., Nicholson, J., Read, B., Kamerlin, S. C. L. & da Silva, R. G., 9 Dec 2022, In: Nature Communications. 13, 15 p., 7607.
Research output: Contribution to journal › Article › peer-review
Open access

Structure, dynamics, and molecular inhibition of the Staphylococcus aureus m¹A22-tRNA methyltransferase TrmK
Sweeney, P., Galliford, A., Kumar, A., Raju, D., Krishna, N. B., Sutherland, E., Leo, C. J., Fisher, G., Lalitha, R., Muthuraj, L., Sigamani, G., Oehler, V., Synowsky, S. A., Shirran, S. L., Gloster, T., Melo Czekster, C., Kumar, P. & da Silva, R. G., May 2022, In: Journal of Biological Chemistry. 298, 6, 15 p., 102040.
Research output: Contribution to journal › Article › peer-review

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