NMR and Structural Studies
Prof G M Blackburn
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| 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. |
KeywordsEnzyme 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 outlineMy 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 fugitive “metaphosphate” in several enzyme-catalysed phosphoryl transfer reactions has been amply validated for an expanding number of phosphatases and both metabolic and signalling kinases. 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 engendered the 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. |
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Selected PublicationsPrioritization 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 |
| Novel diadenosine polyphosphate analogs with oxymethylene bridges replacing oxygen in the polyphosphate chain: potential substrates and/or inhibitors of Ap4A hydrolases. Guranowski A, Starzynska E, Pietrowska-Borek M, Rejman D, Blackburn GM, FEBS Journal (2009) 276(6) 1546-1553 |
| Determination of the microscopic equilibrium dissociation constants for risedronate and its analogues reveals two distinct roles for the nitrogen atom in nitrogen-containing bisphosphonate drugs. Hounslow A, Carran J, Brown RJ, Rejman D, Blackburn GM, Watts DJ, J. Med. Chem. (2008) 51(14) 4170-4178 |
| Anionic charge is prioritized over geometry in aluminum and magnesium fluoride transition state analogs of phosphoryl transfer enzymes. Baxter NJ, Blackburn GM, Marston JP, Hounslow AM, Cliff MJ, Bermel W, Williams NH, Hollfelder F, Wemmer DE, Waltho JP, J. Amer. Chem. Soc. (2008) 130(12) 3952-3958 |
| 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 |