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Prof G M Blackburn

Sheffield 222 9462
email - G.M.Blackburn@sheffield.ac.uk

Professor of Chemical Biology: BA Cambridge (1956); MA Cambridge (1961); PhD Nottingham (1960); Cambridge University Demonstrator (1961-65); C.Chem. FRSC. Cambridge University Demonstrator (1961-65); Visiting Biochemistry Professor Brandeis University (1966-67); Jeffery Lecturer University of NSW (1991); Visiting Professor Okayama University (1994); Chairman IUPAC Division-III Biomolecular Chemistry, 2005-2007; Titular Member IUPAC Division-III, 2012-14; Arbusov Medal and Prize, 2011.

Keywords

Enzyme mechanisms; transition states and transition state analogues; phosphoryl transfer mechanisms; biological phosphorus chemistry; nucleotide analogues; DNA repair enzymes; stable analogues of S-adenosyl methionine.

Research outline

My work in chemical biology is directed at recognition processes between small and large biological molecules. It seeks an understanding of mechanisms of biological processes at atomic resolution and its application to medical problems and drug design. This work has thereby identified new targets for organic synthesis and quantitative evaluation of their behaviour in a protein context.

Our controversial (2003) proposal that trifluoromagnesate is an isosteric and isoelectronic transition state analogue of the putative “metaphosphate” in several enzyme-catalysed phosphoryl transfer reactions has been amply validated for an expanding number of phosphatases, both metabolic and signalling kinases, G proteins, and membrane ATP-driven protein pumps. Its application to understanding the atomic details of the amazingly facile manipulation of phosphate esters and anhydrides by enzymes across a wide spectrum of reaction types has been rationalised in the dual concepts of the “Anionic Shield” and of “Charge Balance”. This work is providing a new understanding of the evolutionary inevitability of phosphates for their truly Universal roles in the Chemistry of Life.

This research led to the Award of the Arbuzovs Prize and Medal in Russia in 2011, the first time it has been received by a UK scientist.

Mike Blackburn receiving the Arbosov medal

Selected Publications

Chemical polysialylation of human recombinant butyrylcholinesterase delivers a long-acting bioscavenger for nerve agents in vivo. Ilyushin DG, Smirnov IV, Belogurov AA, Dyachenko IA, Zharmukhamedova TL, Novozhilova TI, Bychikhin EA, Serebryakova MV, Kharybib ON, Murashev AN, Anikienko KA, Nikolaev EN, Ponomarenko NA, Genkin DD, Blackburn GM, Masson P, Gabibov AG, Proc. Nat. Acad. Sci. USA (2013) 110(4) 1243-1248
Charge-balanced metal fluoride complexes for protein kinase A with adenosine diphosphate and substrate peptide SP20. Jin Y, Cliff MJ, Baxter NJ, Dannatt HRW, Hounbslow AM, Bowler MW, Blackburn GM, Waltho JP. Angew. Chem. Int. Ed. (2012) 49 12408-12411
Reflections on biocatalysis involving phosphorus. Blackburn GM, Bowler MW, Jin Y, Waltho JP. Biochemistry (Moscow) (2012) 77(10) 1083-1096
Near attack conformers dominate β-phosphoglucomutase complexes where geometry and charge distribution reflect those of substrate, Griffin JL, Bowler MW, Baxter NJ, Leigh KN, Dannatt HRW, Hounslow AM, Blackburn GM, Webster CE, Cliff MJ, Waltho JP Proc Nat. Acad. Sci. USA (2012) 109(18) 6910-6915
Prioritization of Charge over Geometry in Transition State Analogues of a Dual Specificity Protein Kinase. Liu XX, Marston JP, Baxter NJ, Hounslow AM, Zhao YF, Blackburn GM, Cliff MJ, Waltho JP. J. Amer. Chem. Soc., 2011 133(7) 3989–3994
Transition State Analogue Structures of Human Phosphoglycerate Kinase Establish the Importance of Charge Balance in Catalysis. Cliff MJ, Bowler MW, Varga A, Marston JP, Szabo J, Hounslow AM, Baxter NJ, Blackburn GM, Vas M, Waltho JP. J. Am. Chem. Soc., 2010, 132(18), 6507–6516
Why did Nature select phosphate for its dominant roles in biology? Bowler MW, Cliff MJ, Waltho JP, Blackburn GM. New J. Chem., 2010, 34, 784-794
Atomic details of near-transition state conformers for enzyme phosphoryl transfer revealed by MgF3- rather than by phosphoranes. Baxter NJ, Bowler MW, Alizadeh T, Cliff MJ, Hounslow AM, Wu B, Berkowitz DB, Williams NH, Blackburn GM, Waltho, JP, Proc Nat. Acad. Sci. USA, EE (2010) Feb 17, 2010 1-6
Structural tightening and interdomain communication in the catalytic cycle of phosphoglycerate kinase. Marston JP, Cliff MJ, Reed MAC, Blackburn GM, Hounslow AM, Craven CJ, Waltho JP, J. Mol. Biol. (2010) 396(2) 345-360
MgF3- and β-galactose 1-phosphate in the active site of β-phosphoglucomutase form a transition state analogue of phosphoryl transfer. Baxter NJ, Hounslow AM, Bowler MW, Williams NH, Blackburn GM, Waltho JP. J. Amer. Chem. Soc. (2009) 131(45) 16334-16335
Nucleic acids in chemistry and biology, 3rd Ed. Blackburn GM, Gait MJ, Loakes D, Williams DM, Eds. UK. (2006) 470 pp, Roy. Soc. Chem. Cambridge UK