Professor Chris Schofield, FRS
Professor of Organic ChemistryÂ
Senior Research Fellow in Chemistry
Chris is Head of Organic Chemistry at the University of Oxford. He supervises research students and postdoctoral workers in the general field of Chemical Biology and is involved in several doctoral training programmes.
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Research interests
Research in our group aims to contribute to a chemical understanding of biological systems, where possible of medicinal or agricultural importance. We have a particular interest in metallo-enzymes that are included in antibiotic biosynthesis and resistance as well as in human physiology. The iron and zinc dependent enzymes we study are of intrinsic chemical interest because they can catalyse reactions impossible for synthetic chemistry. Some of them also play roles in human physiology and disease, e.g. in enabling us to respond to limiting oxygen availability and to repair damage to our DNA. We are presently interested in understanding the details of how environmental factors regulate gene expression, with a particular focus on oxygen regulated processes. We are a highly collaborative group, often working with researchers in academia and industry.
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Related websites
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Publications
2015
443.   Identification of a pathogenic FTO mutation by next-generation sequencing in a newborn with growth retardation and developmental delay. Daoud H, Zhang D, McMurray F, Yu A, Luco SM, Vanstone J, Jarinova O, Carson N, Wickens J, Shishodia S, Choi H, McDonough MA, Schofield CJ, Harper ME, Dyment DA, Armour, C. M. (2015).
Journal of Medical Genetics. 2015,
442.  Quantifying the Binding Interaction between the Hypoxia-Inducible Transcription Factor and the von Hippel-Lindau Suppressor. Domene C, Jorgensen C, Vanommeslaeghe K, Schofield CJ, Jr MA (2015).
Journal of Chemical Theory and Computation, 2015, 11(8), 3946-3954.
441.  Rationally engineered flavin-dependent oxidase reveals steric control of dioxygen reduction. Zafred D, Steiner B, Teufelberger AR, Hromic A, Karplus PA, Schofield CJ, Wallner S, Macheroux, P.
FEBS Journal, 2015, 282(16), 3060-3074.
440.  The broad spectrum 2-oxoglutarate oxygenase inhibitor N-oxalylglycine is present in rhubarb and spinach leaves. Al-Qahtani K, Jabeen B, Sekirnik R, Riaz N, Claridge TD, Schofield CJ, McCullagh JS.
Phytochemistry, 2015, 117, 456-461. doi:10.1016/j.phytochem.2015.06.028
439.  Protein Hydroxylation Catalyzed by 2-Oxoglutarate-dependent Oxygenases. Markolovic S, Wilkins SE, Schofield C J.
The Journal of Biological Chemistry, 2015, 290(34), 20712-20722.
438.  Design and synthesis of potent and selective inhibitors of BRD7 and BRD9 bromodomains. Hay DA, Rogers CM, Fedorov O, Tallant C, Martin S, Monteiro OP, Mueller S, Knapp S, Schofield CJ, Brennan PE.
MedChemComm, 2015, 6(7), 1381-1386.
437.  Assay for drug discovery: Synthesis and testing of nitrocefin analogues for use as β-lactamase substrates. Ghavami A, Labbé G, Brem J, Goodfellow VJ, Marrone L, Tanner CA, King DT, Lam M, Strynadka NC, Pillai DR, Siemann S, Spencer J, Schofield CJ, Dmitrienko GI, Analytical Biochemistry, 2015, 486, 75-77.
436.  Kinetic Investigations of the Role of Factor Inhibiting Hypoxia-inducible Factor (FIH) as an Oxygen Sensor. Tarhonskaya H, Hardy AP, Howe EA, Loik ND, Kramer HB, McCullagh JS, Schofield CJ, Flashman E,  The Journal of Biological Chemistry, 2015, 290(32), 19726-19742.
435.  Expanding the yeast protein arginine methylome.
Plank M, Fischer R, Geoghegan V, Charles PD, Konietzny R, Acuto O, Pears C, Schofield CJ, Kessler BM.
Proteomics, 2015,
434. The oxygenase Jmjd6-a case study in conflicting assignments.
Böttger A, Islam MS, Chowdhury R, Schofield CJ, Wolf A.
The Biochemical Journal, 2015, 468(2), 191-202.
433.   Structure of the ribosomal oxygenase OGFOD1 provides insights into the regio- and stereoselectivity of prolyl hydroxylases.
Horita S, Scotti JS, Thinnes C, Mottaghi-Taromsari YS, Thalhammer A, Ge W, Aik W, Loenarz C, Schofield CJ, McDonough MA.
Structure, 2015, 23(4), 639-652.
432.  Emulsion PCR significantly improves nonequilibrium capillary electrophoresis of equilibrium mixtures-based aptamer selection: allowing for efficient and rapid selection of aptamer to unmodified ABH2 protein.
Yufa R, Krylova SM, Bruce C, Bagg EA, Schofield CJ, Krylov SN.
Analytical chemistry, 2015, 87(2), 1411-1419.
431. Studying the active-site loop movement of the São Paolo metallo-β-lactamase-1.
Brem J, Struwe WB, Rydzik AM, Tarhonskaya H, Pfeffer I, Flashman E, Van Berkel SS, Spencer J, Claridge TDW, McDonough MA, Benesch JLP, Schofield CJ.
Chemical Science, 2015, 6(2), 956-963.
430. Crystal Structure of Human Persulfide Dioxygenase: Structural Basis of Ethylmalonic Encephalopathy
Pettinati I, Brem J, McDonough MA, Schofield CJ.
Human molecular genetics, 2015, 24(1), 1-12
429. Adipocyte Pseudohypoxia Suppresses Lipolysis and Facilitates Benign Adipose Tissue Expansion
Michailidou Z, Morton NM, Moreno Navarrete JM, West CC, Stewart KJ, Fernández-Real JM, Schofield CJ, Ratcliffe PJ.
Diabetes, 2015, 64:3 733-745.
428. Biochemical characterization of New Delhi metallo-β-lactamase variants reveals differences in protein stability
Makena A, Brem J, Pfeffer I, Geffen RE, Wilkins SE, Tarhonskaya H, Flashman E, Phee LM, Wareham DW, Schofield, CJ
The Journal of antimicrobial chemotherapy, 2015, 70(2), 463-469.  doi: 10.1093/jac/dku403.
2014
427. . Studies on the catalytic domains of multiple JmjC oxygenases using peptide substrates. Williams ST, Walport LJ, Hopkinson RJ, Madden SK, Chowdhury R, Schofield CJ, Kawamura A. Epigenetics : official journal of the DNA Methylation Society, 2014, 9(12), 1596-1603.
426. Conformational studies on substituted epsilon-caprolactams by X-ray crystallography and NMR spectroscopy
Gruber T, Thompson AL, Odell B, Bombicz P, Schofield CJ.
New Journal of Chemistry, 2014, 38(12), 5905-5917.
425. Optimisation of a triazolopyridine based histone demethylase inhibitor yields a potent and selective KDM2A (FBXL11) inhibitor.
England KS, Tumber A, Krojer T, Scozzafava G, Ng SS, Daniel M, Szykowska A, Che K, von Delft F, Burgess-Brown NA, Kawamura A, Schofield CJ, Brennan PE.
MedChemComm, 2014, 5(12), 1879-1886.
424. Oxygenase-Catalyzed Desymmetrization of N,N-Dialkyl-piperidine-4-carboxylic Acids.
Rydzik A M, Leung IKH, Kochan GT, McDonough M A, Claridge TDW, Schofield CJ.  Angewandte Chemie-International Edition, 2014, 53(41), 10925-10927.
423. Replying to B. Heinemann et al. Nature 514, http://dx.doi.org/10.1038/nature13688
Kruidenier L, Chung, C. W., Cheng, Z., Liddle, J, Che K, Joberty G, Bantscheff M, Bountra C, Bridges A, Diallo H, Eberhard D, Hutchinson S, Jones E, Katso R, Leveridge M, Mander PK, Mosley J, Ramirez-Molina C, Rowland P, Schofield CJ, Sheppard RJ, Smith JE, Swales C, Tanner R, Thomas P, Tumber A, Drewes G, Oppermann U, Patel DJ, Lee K, Wilson DM.
Kruidenier et al. reply.
Nature, 2014, 514 7520, E2.
422. Rhodanine hydrolysis leads to potent thioenolate mediated metallo-β-lactamase inhibition.
Brem J, van Berkel SS, Aik WS, Rydzik AM, Avison MB, Pettinati I, Umland K-D, Kawamura A, Spencer J, Claridge TDW, McDonough MA, Schofield CJ
Nature Chemistry, 2014, 6, 1084-1090.
421. Ejection of structural zinc leads to inhibition of Îł-butyrobetaine hydroxylase
Rydzik AM, Brem J, Struwe WB, Kochan GT, Benesch JL, Schofield CJ
Bioorganic & Medicinal Chemistry Letters, 2014, 24, 4954-4957.
420. Investigating the contribution of the active site environment to the slow reaction of hypoxia-inducible factor prolyl hydroxylase domain 2 with oxygen
Tarhonskaya H, Chowdhury R, Leung IK, Loik ND, McCullagh JS, Claridge TD, Schofield CJ, Flashman E
Biochemical Journal, 2014, 463, 363-372.
419. Oxygenase-Catalyzed Desymmetrization of N,N-Dialkyl-piperidine-4-carboxylic Acids
Rydzik AM, Leung IKAdditional author information:
Identifier: §ORCiD ID: 0000-0003-0633-6771
, Kochan GT, McDonough MA, Claridge TD, Schofield CJAngewandte Chemie, 2014, 53,10925-10927.
418. Human oxygen sensing may have origins in prokaryotic elongation factor Tu prolyl-hydroxylation
Scotti JS, Leung IK, Ge W, Bentley MA, Paps J, Kramer HB, Lee J, Aik W, Choi H, Paulsen SM, Bowman LA, Loik ND, Horita S, Ho CH, Kershaw NJ, Tang CM, Claridge TD, Preston GM, McDonough MA, Schofield CJ
PNAS, 2014, 111, 13331-13336.
417. Jumonji domain containing protein 6 (Jmjd6) modulates splicing and specifically interacts with arginine-serine-rich (RS) domains of SR- and SR-like proteins.
Heim A, Grimm C, Müller U, Häußler S, Mackeen MM, Merl J, Hauck SM, Kessler BM, Schofield CJ, Wolf A, Böttger A
Nucleic Acids Research, 2014, 42, 7833-7850.
416. Comparison of the substrate selectivity and biochemical properties of human and bacterial Îł-butyrobetaine hydroxylase
Rydzik AM, Leung IK, Kochan GT, Loik ND, Henry L, McDonough MA, Claridge TD, Schofield CJ
Organic & Biomolecular Chemistry, 2014, 12, 6354-6358.
415. Pro-angiogenic effects of proly-hydroxylase inhibitor FG-2216 and potential for use in a novel strategy of therapeutic angiogenesis for difficult cases of coronary total occlusion
Barnett G, Kelly D, Flashman E, Schofield C, Gershlick A
Angiogenesis, 2014, 17, 740-740.
414. Discovery and Optimization of Small-Molecule Ligands for the CBP/p300 Bromodomains
Hay DA, Fedorov O, Martin S, Singleton DC, Tallant C, Wells C, Picaud S, Philpott M, Monteiro OP, Rogers CM, Conway SJ, Rooney TP, Tumber A, Yapp C, Filippakopoulos P, Bunnage ME, MĂĽller S, Knapp S, Schofield CJ, Brennan PE
JACS, 2014, 136, 9308-9319.
413. Inhibition of the HIF1α-p300 interaction by quinone- and indandione-mediated ejection of structural Zn(II)
Jayatunga MKP, Thompson S, McKee TC, Chan MC, Reece KM, Hardy AP, Sekirnik R, Seden PT, Cook KM, McMahon JB, Figg WD, Schofield CJ, Hamilton AD
European Journal of Medicinal Chemistry, 2014, In Press.
412. HIF prolyl hydroxylase inhibition prior to transient focal cerebral ischaemia is neuroprotective in mice
Chen RL, Ogunshola OO, Yeoh KK, Jani A, Papadakis M, Nagel S, Schofield CJ, Buchan AM
J. Neurochem, 2014, 131, 177-189.
411. Ribosomal oxygenases are structurally conserved from prokaryotes to humans
Chowdhury R, Sekirnik R, Brissett NC, Krojer T, Ho CH, Ng SS, Clifton IJ, Ge W, Kershaw NJ, Fox GC, Muniz JR, Vollmar M, Phillips C, Pilka ES, Kavanagh KL, von Delft F, Oppermann U, McDonough MA, Doherty AJ, Schofield CJ
Nature, 2014, 510, 422-426.
410. Targeting Histone Lysine Demethylases – Progress, Challenges, and the Future
Thinnes CC, England KS, Kawamura A, Chowdhury R, Schofield CJ, Hopkinson RJ
Biochimica et Biophysica Acta, 2014. 1839(12), 1416-1432
409. Human UTY(KDM6C) is a Male-Specific N{epsilon}-Methyl Lysyl-Demethylase
Walport LJ, Hopkinson RJ, Vollmar M, Madden SK, Gileadi C, Oppermann U, Schofield CJ, Johansson C
Journal of Biological Chemistry, 2014, 289, 18302-18313.
408. A code for RanGDP binding in ankyrin repeats defines a nuclear import pathway
Lu M, Zak J, Chen S, Sanchez-Pulido L, Severson DT, Endicott J, Ponting CP, Schofield CJ, Lu X
Cell, 2014, 157, 1130-1145.
407. Modulating carnitine levels by targeting its biosynthesis – selective inhibition of gamma-butyrobetaine hydroxylase
Rydzik AM, Chowdhury R, Kochan GT, Williams ST, McDonough MA, Kawamura A, Schofield CJ
Chemical Science, 2014, 5, 1765-1771.
406. Structures of human ALKBH5 demethylase reveal a unique binding mode for specific single stranded m6A RNA demethylation
Xu C, Liu K, Tempel W, Demetriades M, Aik W, Schofield CJ, Min J
Journal of Biological Chemistry, 2014, 289, 17299-17311.
405. Structure of human RNA N6-methyladenine demethylase ALKBH5 provides insights into its mechanisms of nucleic acid recognition and demethylation
Aik W, Scotti JS, Choi H, Gong L, Demetriades M, Schofield CJ, McDonough MA
Nucleic Acids Res., 2014, 42, 4741-4754.
404. Studies on deacetoxycephalosporin C synthase support a consensus mechanism for 2-oxoglutarate dependent oxygenases
Tarhonskaya H, Szollossi A, Leung IKH, Bush JT, Henry L, Chowdhury R, Iqbal A, Claridge, TDW, Schofield CJ, Flashman E
Biochemistry, 2014, 53, 2483-2493.
403. Monitoring conformational changes in the NDM-1 metallo-β-lactamase by 19F NMR spectroscopy
Rydzik AM, Brem J, van Berkel SS, Pfeffer I, Makena A, Claridge TD, Schofield CJ
Angewandte Chemie Int. Ed., 2014, 53, 3129-3133.
402. Non-enzymatic chemistry enables 2-hydroxyglutarate-mediated conversion of 2-oxoglutarate oxygenases
Tarhonskaya H, Rydzik AM, Leung IKH, Loik ND, Chan MC, Kawaura A, McCullagh JSO, Claridge TDW, Flashman E, Schofield CJ
Nature Communications, 2014, 5, 3423.
401. OGFOD1 catalyzes prolyl hydroxylation of RPS23 and is involved in translation control and stress granule formation
Singleton RS, Liu-Yi P, Formenti F, Ge W, Sekirnik R, Fischer R, Adam J, Pollard PJ, Wolf A, Thalhammer A, Loenarz C, Flashman E, Yamamoto A, Coleman ML, Kessler BM, Wappner P, Schofield CJ, Ratcliffe PJ, Cockman ME
Proc Natl Acad Sci U S A., 2014, 111, 4031-4036.
400. Sudestada1, a Drosophila ribosomal prolyl-hydroxylase required for mRNA translation, cell homeostasis, and organ growth
Katz MJ, Acevedo JM, Loenarz C, Galagowsy D, Liu-Yi P, Pérez-Pepe M, Thalhammer A, Sekirnik R, Ge W, Melani M, Thomas MG, Simonetta S, Boccaccio GL, Schofield CJ, Cockman ME, Ratcliffe PJ, Wappner P
Proc Natl Acad Sci USA, 2014, 111, 4025-4030.
399. The Prolyl Hydroxylase Inhibitor BIQ/FG-2216 Stabilises HIF-1 alpha and Upregulates VEGF in vitro: A Potential Strategy For Difficult CTO Lesions in Patients
Barnett GA, Flashman E, Kelly DJ, Schofield CJ, Gershlick A
Journal of the American College of Cardiology, 2014, 62, B119.
398. Hydroxylation of the eukaryotic ribosomal decoding center affects translational accuracy
Loenarz C, Sekirnik R, Thalhammer A, Ge W, Spivakovsky E, Mackeen MM, McDonough MA, Cockman ME, Kessler BM, Ratcliffe PJ, Wolf A, Schofield CJ
Proc Natl Acad Sci U S A, 2014, 111, 4019-4024.
397. Pan-Histone Demethylase Inhibitors Simultaneously Targeting Jumonji C and Lysine Specific Demethylases Display High Anticancer Activities
Rotili D, Tomassi S, Conte M, Benedetti R, Tortorici M, Ciossani G, Valente S, Marrocco B, Labella D, Novellino E, Mattevi A, Altucci L, Tumber A, Yapp C, King ON, Hopkinson RJ, Kawamura A, Schofield CJ, Mai A, J Med Chem, 2014, 57, 42-55.
396. A Cell-Permeable Ester Derivative of the JmjC Histone Demethylase Inhibitor IOX1
Schiller R, Scozzafava G, Tumber A, Wickens JR, Bush JT, Rai G, Lejeune C, Choi H, Yeh TL, Chan MC, Mott BT, McCullagh JS, Maloney DJ, Schofield CJ, Kawamura A
ChemMedChem., 2014, 9, 566-571.
395. Optimal Translational Termination Requires C4 Lysyl Hydroxylation of eRF1
Feng T, Yamamoto A, Wilkins SE, Sokolova E, Yates LA, Münzel M, Singh P, Hopkinson RJ, Fischer R, Cockman ME, Shelley J, Trudgian DC, Schödel J, McCullagh JS, Ge W, Kessler BM, Gilbert RJ, Frolova LY, Alkalaeva E, Ratcliffe PJ, Schofield CJ, Coleman ML
Mol Cell, 2014, 53, 645-654.
394. Fluoromethylated derivatives of carnitine biosynthesis intermediates – synthesis and applications
Rydzik A M, Leung IK, Thalhammer A, Kochan GT, Claridge TD, Schofield CJ
Chem Commun, 2014, 50, 1175-1177.