Dr Rafael Guimaraes da Silva

Research Fellow

Researcher profile

Phone

+44 (0)1334 463496

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

• Benjamin Read
• Teresa Filipa Guerreiro Machado
• Gemma Fisher

Selected publications

• An exceptionally potent inhibitor of human CD73

  Bowman, C. E., da Silva, R. G., Pham, A. & Young, S. W., 6 Aug 2019, In : Biochemistry. 58, 31, p. 3331-3334 4 p.

  Research output: Contribution to journal ? Article

• Mapping the structural path for allosteric inhibition of a short-form ATP phosphoribosyltransferase by histidine

  Thomson, C. M., Alphey, M. S., Fisher, G. & da Silva, R. G., 16 Jul 2019, In : Biochemistry. 58, 28, p. 3078-3086

  Research output: Contribution to journal ? Article

• Allosteric activation shifts the rate-limiting step in a short-form ATP phosphoribosyltransferase

  Fisher, G., Thomson, C. M., Stroek, R., Czekster, C. M., Hirschi, J. S. & da Silva, R. G., 24 Jul 2018, In : Biochemistry. 57, 29, p. 4357-4367

  Research output: Contribution to journal ? Article

• Catalytic and anticatalytic snapshots of a short-form ATP phosphoribosyltransferase

  Alphey, M. S., Fisher, G., Ge, Y., Gould, E. R., Guerreiro Machado, T. F., Liu, H., Florence, G. J., Naismith, J. H. & da Silva, R. G., 1 Jun 2018, In : ACS Catalysis. 8, 6, p. 5601-5610 10 p.

  Research output: Contribution to journal ? Article

• Discovery of trifluoromethyl glycol carbamates as potent and selective covalent monoacylglycerol lipase (MAGL) inhibitors for treatment of neuroinflammation

  McAllister, L., Butler, C., Mente, S., O'Neil, S. V., Fonseca, K., Piro, J., Cianfrogna, J., Foley, T., Gilbert, A., Harris, A., Helal, C. J., Johnson, D. S., Montgomery, J. I., Nason, D. M., Noell, S., Pandit, J., Rogers, B. N., Samad, T. A., Shaffer, C. L., da Silva, R. G., Uccello, D. P., Webb, D. & Brodney, M. A., 12 Apr 2018, In : Journal of Medicinal Chemistry. 61, 7, p. 3008?3026

  Research output: Contribution to journal ? Article

• Linear Eyring plots conceal a change in rate-limiting step in an enzyme reaction

  Machado, T. F. G., Gloster, T. & da Silva, R. G., 11 Dec 2018, In : Biochemistry. 57, 49, p. 6757-6761

  Research output: Contribution to journal ? Article

• Kinetics and structure of a cold-adapted hetero-octameric ATP phosphoribosyltransferase

  Stroek, R., Ge, Y., Talbot, P. D., Glok, M. K., Bernas, K. E., Thomson, C. M., Gould, E. R., Alphey, M. S., Liu, H., Florence, G. J., Naismith, J. H. & da Silva, R. G., 7 Feb 2017, In : Biochemistry. 56, 5, p. 793-803 11 p.

  Research output: Contribution to journal ? Article

• A continuous and direct assay to monitor leucine-rich repeat kinase 2 activity

  Silva, R. G., Geoghegan, K. F., Qiu, X. & Aulabaugh, A., 2014, In : Analytical Biochemistry. 450, 1, p. 63-69

  Research output: Contribution to journal ? Article

• Selective mitochondrial staining with small fluorescent probes: importance, design, synthesis, challenges and trends for new markers

  Neto, B. AD., Correa, J. R. & Silva, R. G., 2013, In : RSC Advances. 3, p. 5291-5301

  Research output: Contribution to journal ? Article

• The Biginelli reaction with an imidazolium-tagged recyclable iron catalyst: kinetics, mechanism, and antitumoral activity

  Ramos, L. M., Guido, B. C., Nobrega, C. C., Correa, J. R., Silva, R. G., de Oliveira, H. CB., Gomes, A. F., Gozzo, F. C. & Neto, B. AD., 2013, In : Chemistry - A European Journal. 19, p. 4156-4168

  Research output: Contribution to journal ? Article

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