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Christopher J. Schofield

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For the Yorkshire cricketer, see Chris Schofield (Yorkshire cricketer). For the former England cricketer, see Chris Schofield.

Christopher J. Schofield
Born
Christopher Joseph Schofield

(1960-06-17) 17 June 1960 (age 64)
United Kingdom
NationalityBritish
Other namesChris Schofield, CJS
Alma materUniversity of Manchester (BSc) University of Oxford (DPhil)
AwardsFellow of the Royal Society
Scientific career
FieldsHypoxic Response, Epigenetic, Oxygenases, Antibiotic Resistance
InstitutionsChemistry Research Laboratory, University of Oxford
Websitehttp://schofield.chem.ox.ac.uk/home http://research.chem.ox.ac.uk/christopher-schofield.aspx

Christopher Joseph Schofield (also known as Chris Schofield) is a Professor of Chemistry at the University of Oxford[1] and a Fellow of the Royal Society. Chris Schofield is a professor of organic chemistry at the University of Oxford, Department of Chemistry[2] and a Fellow of Hertford College.[3] Schofield studied functional, structural and mechanistic understanding of enzymes that employ oxygen and 2-oxoglutarate as a co-substrate.[4] His work has opened up new possibilities in antibiotic research,[5] oxygen sensing,[6] and gene regulation.[7]

After work on plant and microbial oxygenases,[4] he studied uncharacterised human oxygenases.[8] His research has identified unanticipated roles for oxygenases[9] in regulating gene expression, importantly in the cellular hypoxic response,[10] and has revealed new post-translational modifications to chromatin and RNA splicing proteins.[11] The work has identified new opportunities for medicinal intervention.[12]

Education

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Chris Schofield attended St Anselm's College catholic grammar school in Merseyside, then studied for a Bachelor of Science in chemistry at the University of Manchester and graduated with a first class honour (1979–1982). In 1982, he moved to Oxford to study for a DPhil with Professor Jack E. Baldwin. In 1985, he became a Departmental Demonstrator in the Dyson Perrins Laboratory, Oxford University followed by his appointment as a Lecturer in Chemistry[2] and a Fellow of Hertford College[3] in 1990. In 1998, he became professor of Chemistry,[1] and in 2011 he was appointed the Head of Organic Chemistry[13] at the Department of Chemistry, University of Oxford. In 2013, he was elected a Fellow of the Royal Society, FRS.[14]

Research

[edit]

The work in laboratory of Chris Schofield focuses on different areas of research, including:

Molecular Mechanisms of the Hypoxic Response

[edit]

Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric α,β-transcriptional complex[15] that mediates the cellular response to oxygen availability in multi-cellular organisms,[6][16] ranging from the simplest known animal Trichoplax adhaerens to humans.[4][6][17][18][19] Investigating the structures and mechanisms of the HIF prolyl hydroxylases is a current focus of the work.[10][20] The group solved crystal structures of PHD2[9][21] - one of the human prolyl hydroxylases - and discovered that the HIF asparaginyl hydroxylase also catalyses hydroxylation of conserved motifs,[22] the ankyrin repeat domain.

Chemical Basis of Epigenetics

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A current focus of the group is modification of histones, in particular oxygenase catalysed N-demethylation of histone methylated-lysine residues[7][23] – in collaboration with the Structural Genomics Consortium. The histone demethylases[24][25] are of interest both with respect to their links to diseases, including cancer[26][27] and inflammatory diseases,[28] as well as the role of methylation in transcriptional regulation.[29] Recent areas of interest include the fat mass and obesity protein[30][31] which was shown to be a nucleic acid demethylase[32] and JMJD6[33][34] which is a lysyl hydroxylase modifying RNA splicing protein.[11]

Structural and Functional Studies on 2OG Oxygenases

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The 2-oxoglutarate (2OG)-dependent oxygenases are a superfamily of non-haem iron dependent oxygenases,[35] most of which use the Krebs cycle intermediate, 2OG, as a co-substrate.[36] The group are interested in understanding these enzymes[37] for their ability to catalyse synthetically difficult or 'impossible' reactions (e.g. the stereoselective hydroxylation of unactivated carbon-hydrogen bonds), for their diverse physiological roles,[8] and for their links to disease.[38] The research focuses on members of the family that are linked to disease, or can be targeted for the treatment of disease.[39][40] Techniques involved in this interdisciplinary research include proteomics,[41] X-ray crystallography,[42] nuclear magnetic resonance (NMR) spectroscopy,[43][44][45][46][47] biological mass spectrometry,[48] molecular biology,[49] enzyme kinetics,[50][51] protein-directed dynamic combinatorial chemistry[52][53] and organic synthesis/medicinal chemistry.[54][55]

Antibiotics: Biosynthesis and Resistance Mechanisms

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Most clinically used antibiotics are based upon natural products.[5] The most important family of antibiotics contains a β-lactam ring, and includes the penicillin,[56] cephalosporin, clavam,[57] and carbapenem[58] antibiotics. The group's biosynthetic work has focused on the clavams[59] and carbapenems,[58] with a particular focus being on the mechanism and structures of enzymes that catalyse chemically 'interesting' steps.[60][61] The biggest threat to the continued use of β-lactam antibiotics is that of bacterial resistance. Schofield is currently working on the design and synthesis of enzyme inhibitors[62][63][64][65] for the metallo β-lactamases[66] – there are no clinically used inhibitor[67] of these enzymes but they pose a significant threat as they catalyse the hydrolysis of almost all clinically used β-lactam antibiotics.[68] A particular interest involves human metallo β-lactamases which share the same fold.[69]

Awards and honours

[edit]

2015-2020: Wellcome Trust Advanced Investigator Award (with Sir Peter Ratcliffe)

2013: Fellow of the Royal Society (London);[14] Member of EMBO; Fellow of the Royal Society of Biology, UK; Member of the Biochemical Society; Member of the Society for Experimental Biology, UK

2012: Finalist – Biotechnology and Biological Sciences Research Council 'Innovator of the Year'[70]

2011: Royal Society of Chemistry, Jeremy Knowles Award, UK;[71] Highly cited paper awards (e.g. Biochemical Journal, Bioorganic & Medicinal Chemistry Letters)

2009 – 2014: PI of ERC Advanced Investigator Grant SPA GA 2008 233240 (with Sir Peter Ratcliffe); Molecular Mechanism of Oxygen Sensing by Enzymes (MOOSE)

2000: Fellow of the Royal Society of Chemistry (London)

References

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  1. ^ a b "Christopher Schofield". University of Oxford. Retrieved 24 July 2023.
  2. ^ a b "Home – Schofield Group". University of Oxford. Retrieved 8 August 2016.
  3. ^ a b "Professor Chris Schofield FRS | Hertford College". University of Oxford. Retrieved 8 August 2016.
  4. ^ a b c Chowdhury, Rasheduzzaman; Sekirnik, Rok; Brissett, Nigel C.; Krojer, Tobias; Ho, Chia-hua; Ng, Stanley S.; Clifton, Ian J.; Ge, Wei; Kershaw, Nadia J. (19 June 2014). "Ribosomal oxygenases are structurally conserved from prokaryotes to humans". Nature. 510 (7505): 422–426. Bibcode:2014Natur.510..422C. doi:10.1038/nature13263. ISSN 0028-0836. PMC 4066111. PMID 24814345.
  5. ^ a b Hamed, Refaat B.; Gomez-Castellanos, J. Ruben; Henry, Luc; Ducho, Christian; McDonough, Michael A.; Schofield, Christopher J. (10 December 2012). "The enzymes of β-lactam biosynthesis". Natural Product Reports. 30 (1): 21–107. doi:10.1039/C2NP20065A. ISSN 1460-4752. PMID 23135477.
  6. ^ a b c Schofield, Christopher J.; Ratcliffe, Peter J. (1 May 2004). "Oxygen sensing by HIF hydroxylases". Nature Reviews Molecular Cell Biology. 5 (5): 343–354. doi:10.1038/nrm1366. ISSN 1471-0072. PMID 15122348. S2CID 6586977.
  7. ^ a b Thinnes, Cyrille C.; England, Katherine S.; Kawamura, Akane; Chowdhury, Rasheduzzaman; Schofield, Christopher J.; Hopkinson, Richard J. (1 December 2014). "Targeting histone lysine demethylases – Progress, challenges, and the future". Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms. Methylation: A Multifaceted Modification – looking at transcription and beyond. 1839 (12): 1416–1432. doi:10.1016/j.bbagrm.2014.05.009. PMC 4316176. PMID 24859458.
  8. ^ a b Horita, Shoichiro; Scotti, John S.; Thinnes, Cyrille; Mottaghi-Taromsari, Yousef S.; Thalhammer, Armin; Ge, Wei; Aik, WeiShen; Loenarz, Christoph; Schofield, Christopher J. (7 April 2015). "Structure of the Ribosomal Oxygenase OGFOD1 Provides Insights into the Regio- and Stereoselectivity of Prolyl Hydroxylases". Structure. 23 (4): 639–652. doi:10.1016/j.str.2015.01.014. PMC 4396695. PMID 25728928.
  9. ^ a b Chowdhury, R; McDonough, MA; Mecinović, J; Loenarz, C; Flashman, E; Hewitson, KS; Domene, C; Schofield, CJ (July 2009). "Structural Basis for Binding of Hypoxia-Inducible Factor to the Oxygen-Sensing Prolyl Hydroxylases". Structure. 17 (7): 981–989. doi:10.1016/j.str.2009.06.002. PMID 19604478.
  10. ^ a b Hon, Wai-Ching; Wilson, Michael I.; Harlos, Karl; Claridge, Timothy D. W.; Schofield, Christopher J.; Pugh, Christopher W.; Maxwell, Patrick H.; Ratcliffe, Peter J.; Stuart, David I. (27 June 2002). "Structural basis for the recognition of hydroxyproline in HIF-1α by pVHL". Nature. 417 (6892): 975–978. Bibcode:2002Natur.417..975H. doi:10.1038/nature00767. ISSN 0028-0836. PMID 12050673. S2CID 4388644.
  11. ^ a b Webby, Celia J.; Wolf, Alexander; Gromak, Natalia; Dreger, Mathias; Kramer, Holger; Kessler, Benedikt; Nielsen, Michael L.; Schmitz, Corinna; Butler, Danica S. (3 July 2009). "Jmjd6 Catalyses Lysyl-Hydroxylation of U2AF65, a Protein Associated with RNA Splicing". Science. 325 (5936): 90–93. Bibcode:2009Sci...325...90W. doi:10.1126/science.1175865. hdl:10033/78493. ISSN 0036-8075. PMID 19574390. S2CID 38938528.
  12. ^ "ReOx Ltd - Oxford Spin-out to Develop New Drug Therapies". Retrieved 8 August 2016.
  13. ^ "SELECTBIO – Epigenetics Speaker Biography". SELECTBIO. Retrieved 8 August 2016.
  14. ^ a b "Christopher Schofield". royalsociety.org. Retrieved 8 August 2016.
  15. ^ Wilkins, Sarah E.; Abboud, Martine I.; Hancock, Rebecca L.; Schofield, Christopher J. (19 April 2016). "Targeting Protein–Protein Interactions in the HIF System". ChemMedChem. 11 (8): 773–786. doi:10.1002/cmdc.201600012. ISSN 1860-7187. PMC 4848768. PMID 26997519.
  16. ^ Jaakkola, Panu; Mole, David R.; Tian, Ya-Min; Wilson, Michael I.; Gielbert, Janine; Gaskell, Simon J.; Kriegsheim, Alexander von; Hebestreit, Holger F.; Mukherji, Mridul (20 April 2001). "Targeting of HIF-α to the von Hippel-Lindau Ubiquitylation Complex by O2-Regulated Prolyl Hydroxylation". Science. 292 (5516): 468–472. Bibcode:2001Sci...292..468J. doi:10.1126/science.1059796. ISSN 0036-8075. PMID 11292861. S2CID 20914281.
  17. ^ Epstein, Andrew C. R.; Gleadle, Jonathan M.; McNeill, Luke A.; Hewitson, Kirsty S.; O'Rourke, John; Mole, David R.; Mukherji, Mridul; Metzen, Eric; Wilson, Michael I. (5 October 2001). "C. elegans EGL-9 and Mammalian Homologs Define a Family of Dioxygenases that Regulate HIF by Prolyl Hydroxylation". Cell. 107 (1): 43–54. doi:10.1016/S0092-8674(01)00507-4. PMID 11595184.
  18. ^ Ge, Wei; Wolf, Alexander; Feng, Tianshu; Ho, Chia-hua; Sekirnik, Rok; Zayer, Adam; Granatino, Nicolas; Cockman, Matthew E.; Loenarz, Christoph (1 December 2012). "Oxygenase-catalyzed ribosome hydroxylation occurs in prokaryotes and humans". Nature Chemical Biology. 8 (12): 960–962. doi:10.1038/nchembio.1093. ISSN 1552-4450. PMC 4972389. PMID 23103944.
  19. ^ Tian, Ya-Min; Yeoh, Kar Kheng; Lee, Myung Kyu; Eriksson, Tuula; Kessler, Benedikt M.; Kramer, Holger B.; Edelmann, Mariola J.; Willam, Carsten; Pugh, Christopher W. (15 April 2011). "Differential Sensitivity of Hypoxia Inducible Factor Hydroxylation Sites to Hypoxia and Hydroxylase Inhibitors". Journal of Biological Chemistry. 286 (15): 13041–13051. doi:10.1074/jbc.M110.211110. ISSN 0021-9258. PMC 3075650. PMID 21335549.
  20. ^ Loenarz, Christoph; Schofield, Christopher J. (1 March 2008). "Expanding chemical biology of 2-oxoglutarate oxygenases". Nature Chemical Biology. 4 (3): 152–156. doi:10.1038/nchembio0308-152. ISSN 1552-4450. PMID 18277970.
  21. ^ McDonough, Michael A.; Li, Vivian; Flashman, Emily; Chowdhury, Rasheduzzaman; Mohr, Christopher; Liénard, Benoît M. R.; Zondlo, James; Oldham, Neil J.; Clifton, Ian J. (27 June 2006). "Cellular oxygen sensing: Crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2)". Proceedings of the National Academy of Sciences. 103 (26): 9814–9819. Bibcode:2006PNAS..103.9814M. doi:10.1073/pnas.0601283103. ISSN 0027-8424. PMC 1502536. PMID 16782814.
  22. ^ Yang, Ming; Chowdhury, Rasheduzzaman; Ge, Wei; Hamed, Refaat B.; McDonough, Michael A.; Claridge, Timothy D. W.; Kessler, Benedikt M.; Cockman, Matthew E.; Ratcliffe, Peter J. (1 April 2011). "Factor-inhibiting hypoxia-inducible factor (FIH) catalyses the post-translational hydroxylation of histidinyl residues within ankyrin repeat domains". FEBS Journal. 278 (7): 1086–1097. doi:10.1111/j.1742-4658.2011.08022.x. ISSN 1742-4658. PMC 3569879. PMID 21251231.
  23. ^ Langley, Gareth W.; Brinkø, Anne; Münzel, Martin; Walport, Louise J.; Schofield, Christopher J.; Hopkinson, Richard J. (25 November 2015). "Analysis of JmjC Demethylase-Catalyzed Demethylation Using Geometrically-Constrained Lysine Analogues". ACS Chemical Biology. 11 (3): 755–762. doi:10.1021/acschembio.5b00738. PMID 26555343. S2CID 19124771.
  24. ^ Walport, Louise J.; Hopkinson, Richard J.; Chowdhury, Rasheduzzaman; Schiller, Rachel; Ge, Wei; Kawamura, Akane; Schofield, Christopher J. (23 June 2016). "Arginine demethylation is catalysed by a subset of JmjC histone lysine demethylases". Nature Communications. 7: 11974. Bibcode:2016NatCo...711974W. doi:10.1038/ncomms11974. PMC 4931022. PMID 27337104.
  25. ^ Ng, Stanley S.; Kavanagh, Kathryn L.; McDonough, Michael A.; Butler, Danica; Pilka, Ewa S.; Lienard, Benoit M. R.; Bray, James E.; Savitsky, Pavel; Gileadi, Opher (5 July 2007). "Crystal structures of histone demethylase JMJD2A reveal basis for substrate specificity". Nature. 448 (7149): 87–91. Bibcode:2007Natur.448...87N. doi:10.1038/nature05971. ISSN 0028-0836. PMID 17589501. S2CID 4331492.
  26. ^ Kawamura, Akane; Loenarz, Christoph; Schofield, Christopher J. (1 September 2011). "Mutations to metabolic enzymes in cancer herald a need to unify genetics and biochemistry". Cell Cycle. 10 (17): 2819–2820. doi:10.4161/cc.10.17.16745. ISSN 1538-4101. PMID 21857150.
  27. ^ Rotili, Dante; Tomassi, Stefano; Conte, Mariarosaria; Benedetti, Rosaria; Tortorici, Marcello; Ciossani, Giuseppe; Valente, Sergio; Marrocco, Biagina; Labella, Donatella (19 December 2013). "Pan-Histone Demethylase Inhibitors Simultaneously Targeting Jumonji C and Lysine-Specific Demethylases Display High Anticancer Activities". Journal of Medicinal Chemistry. 57 (1): 42–55. doi:10.1021/jm4012802. hdl:11573/542432. PMID 24325601.
  28. ^ Kruidenier, Laurens; Chung, Chun-wa; Cheng, Zhongjun; Liddle, John; Che, KaHing; Joberty, Gerard; Bantscheff, Marcus; Bountra, Chas; Bridges, Angela (16 August 2012). "A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response". Nature. 488 (7411): 404–408. Bibcode:2012Natur.488..404K. doi:10.1038/nature11262. ISSN 0028-0836. PMC 4691848. PMID 22842901.
  29. ^ Lercher, Lukas; McDonough, Michael A.; El-Sagheer, Afaf H.; Thalhammer, Armin; Kriaucionis, Skirmantas; Brown, Tom; Schofield, Christopher J. (23 January 2014). "Structural insights into how 5-hydroxymethylation influences transcription factor binding". Chemical Communications. 50 (15): 1794–1796. doi:10.1039/C3CC48151D. ISSN 1364-548X. PMID 24287551. S2CID 6489226.
  30. ^ Church, Chris; Lee, Sheena; Bagg, Eleanor A. L.; McTaggart, James S.; Deacon, Robert; Gerken, Thomas; Lee, Angela; Moir, Lee; Mecinović, Jasmin (14 August 2009). "A Mouse Model for the Metabolic Effects of the Human Fat Mass and Obesity Associated FTO Gene". PLOS Genet. 5 (8): e1000599. doi:10.1371/journal.pgen.1000599. ISSN 1553-7404. PMC 2719869. PMID 19680540.
  31. ^ Aik, WeiShen; Demetriades, Marina; Hamdan, Muhammad K. K.; Bagg, Eleanor. A. L.; Yeoh, Kar Kheng; Lejeune, Clarisse; Zhang, Zhihong; McDonough, Michael A.; Schofield, Christopher J. (23 April 2013). "Structural Basis for Inhibition of the Fat Mass and Obesity Associated Protein (FTO)". Journal of Medicinal Chemistry. 56 (9): 3680–3688. doi:10.1021/jm400193d. PMID 23547775.
  32. ^ Gerken, Thomas; Girard, Christophe A.; Tung, Yi-Chun Loraine; Webby, Celia J.; Saudek, Vladimir; Hewitson, Kirsty S.; Yeo, Giles S. H.; McDonough, Michael A.; Cunliffe, Sharon (30 November 2007). "The Obesity-Associated FTO Gene Encodes a 2-Oxoglutarate-Dependent Nucleic Acid Demethylase". Science. 318 (5855): 1469–1472. Bibcode:2007Sci...318.1469G. doi:10.1126/science.1151710. ISSN 0036-8075. PMC 2668859. PMID 17991826.
  33. ^ Church, Chris; Lee, Sheena; Bagg, Eleanor A. L.; McTaggart, James S.; Deacon, Robert; Gerken, Thomas; Lee, Angela; Moir, Lee; Mecinović, Jasmin (14 August 2009). "A Mouse Model for the Metabolic Effects of the Human Fat Mass and Obesity Associated FTO Gene". PLOS Genet. 5 (8): e1000599. doi:10.1371/journal.pgen.1000599. ISSN 1553-7404. PMC 2719869. PMID 19680540.
  34. ^ Mantri, Monica; Krojer, Tobias; Bagg, Eleanor A.; Webby, Celia J.; Butler, Danica S.; Kochan, Grazyna; Kavanagh, Kathryn L.; Oppermann, Udo; McDonough, Michael A. (13 August 2010). "Crystal Structure of the 2-Oxoglutarate- and Fe(II)-Dependent Lysyl Hydroxylase JMJD6". Journal of Molecular Biology. 401 (2): 211–222. doi:10.1016/j.jmb.2010.05.054. PMID 20685276.
  35. ^ Clifton, Ian J.; McDonough, Michael A.; Ehrismann, Dominic; Kershaw, Nadia J.; Granatino, Nicolas; Schofield, Christopher J. (1 April 2006). "Structural studies on 2-oxoglutarate oxygenases and related double-stranded β-helix fold proteins". Journal of Inorganic Biochemistry. High-valent iron intermediates in biologyHigh-valent iron intermediates in biology. 100 (4): 644–669. doi:10.1016/j.jinorgbio.2006.01.024. PMID 16513174.
  36. ^ Welford, Richard W.D.; Kirkpatrick, Joanna M.; McNeill, Luke A.; Puri, Munish; Oldham, Neil J.; Schofield, Christopher J. (5 December 2005). "Corrigendum to "Incorporation of oxygen into the succinate co-product of iron(II) and 2-oxoglutarate dependent oxygenases from bacteria, plants and humans (FEBS 29930)" [FEBS Lett. 579 (2005) 5170–5174]". FEBS Letters. 579 (29): 6688. doi:10.1016/j.febslet.2005.11.001. hdl:10536/DRO/DU:30095401. ISSN 1873-3468.
  37. ^ Loenarz, Christoph; Mecinović, Jasmin; Chowdhury, Rasheduzzaman; McNeill, LukeA.; Flashman, Emily; Schofield, ChristopherJ. (23 February 2009). "Evidence for a Stereoelectronic Effect in Human Oxygen Sensing". Angewandte Chemie International Edition. 48 (10): 1784–1787. doi:10.1002/anie.200805427. ISSN 1521-3773. PMID 19180614.
  38. ^ Astuti, Dewi; Ricketts, Christopher J.; Chowdhury, Rasheduzzaman; McDonough, Michael A.; Gentle, Dean; Kirby, Gail; Schlisio, Susanne; Kenchappa, Rajappa S.; Carter, Bruce D. (1 February 2011). "Mutation analysis of HIF prolyl hydroxylases (PHD/EGLN) in individuals with features of phaeochromocytoma and renal cell carcinoma susceptibility". Endocrine-Related Cancer. 18 (1): 73–83. doi:10.1677/ERC-10-0113. ISSN 1351-0088. PMC 3006001. PMID 20959442.
  39. ^ Rose, Nathan R.; McDonough, Michael A.; King, Oliver N. F.; Kawamura, Akane; Schofield, Christopher J. (14 July 2011). "Inhibition of 2-oxoglutarate dependent oxygenases". Chemical Society Reviews. 40 (8): 4364–97. doi:10.1039/C0CS00203H. ISSN 1460-4744. PMID 21390379.
  40. ^ Aik, WeiShen; Scotti, John S.; Choi, Hwanho; Gong, Lingzhi; Demetriades, Marina; Schofield, Christopher J.; McDonough, Michael A. (1 April 2014). "Structure of human RNA N6-methyladenine demethylase ALKBH5 provides insights into its mechanisms of nucleic acid recognition and demethylation". Nucleic Acids Research. 42 (7): 4741–4754. doi:10.1093/nar/gku085. ISSN 0305-1048. PMC 3985658. PMID 24489119.
  41. ^ Mackeen, Mukram M.; Kramer, Holger B.; Chang, Kai-Hsuan; Coleman, Matthew L.; Hopkinson, Richard J.; Schofield, Christopher J.; Kessler, Benedikt M. (21 July 2010). "Small-Molecule-Based Inhibition of Histone Demethylation in Cells Assessed by Quantitative Mass Spectrometry". Journal of Proteome Research. 9 (8): 4082–4092. doi:10.1021/pr100269b. PMC 4681095. PMID 20583823.
  42. ^ Clifton, Ian J.; Hsueh, Li-Ching; Baldwin, Jack E.; Harlos, Karl; Schofield, Christopher J. (15 December 2001). "Structure of proline 3-hydroxylase". European Journal of Biochemistry. 268 (24): 6625–6636. doi:10.1046/j.0014-2956.2001.02617.x. ISSN 1432-1033. PMID 11737217.
  43. ^ Mbenza NM, Vadakkedath PG, McGillivray DJ, Leung IK (December 2017). "NMR studies of the non-haem Fe(II) and 2-oxoglutarate-dependent oxygenases". J. Inorg. Biochem. 177: 384–394. doi:10.1016/j.jinorgbio.2017.08.032. PMID 28893416.
  44. ^ Khan A, Leśniak RK, Brem J, Rydzik AM, Choi H, Leung IK, McDonough MA, Schofield CJ, Claridge TD (February 2016). "Development and application of ligand-based NMR screening assays for γ-butyrobetaine hydroxylase". Med. Chem. Commun. 7 (5): 873–880. doi:10.1039/C6MD00004E. hdl:2292/30083.
  45. ^ Leung IK, Demetriades M, Hardy AP, Lejeune C, Smart TJ, Szöllössi A, Kawamura A, Schofield CJ, Claridge TD (January 2013). "Reporter ligand NMR screening method for 2-oxoglutarate oxygenase inhibitors". J. Med. Chem. 56 (2): 547–555. doi:10.1021/jm301583m. PMC 4673903. PMID 23234607.
  46. ^ Leung IK, Flashman E, Yeoh KK, Schofield CJ, Claridge TD (January 2010). "Using NMR solvent water relaxation to investigate metalloenzyme-ligand binding interactions". J. Med. Chem. 53 (2): 867–875. doi:10.1021/jm901537q. PMID 20025281.
  47. ^ Rydzik AM, Leung IK, Thalhammer A, Kochan GT, Claridge TD, Schofield CJ (February 2014). "Fluoromethylated derivatives of carnitine biosynthesis intermediates - synthesis and applications". Chem. Commun. 50 (10): 1175–1177. doi:10.1039/c3cc47581f. PMID 24317009.
  48. ^ Mecinović, Jasmin; Chowdhury, Rasheduzzaman; Flashman, Emily; Schofield, Christopher J. (15 October 2009). "Use of mass spectrometry to probe the nucleophilicity of cysteinyl residues of prolyl hydroxylase domain 2". Analytical Biochemistry. 393 (2): 215–221. doi:10.1016/j.ab.2009.06.029. PMID 19563769.
  49. ^ Tan, SuatCheng; Carr, CarolynA.; Yeoh, KarKheng; Schofield, ChristopherJ.; Davies, KayE.; Clarke, Kieran (1 April 2012). "Identification of valid housekeeping genes for quantitative RT-PCR analysis of cardiosphere-derived cells preconditioned under hypoxia or with prolyl-4-hydroxylase inhibitors". Molecular Biology Reports. 39 (4): 4857–4867. doi:10.1007/s11033-011-1281-5. ISSN 0301-4851. PMC 3294216. PMID 22065248.
  50. ^ Rydzik AM, Leung IK, Kochan GT, Thalhammer A, Oppermann U, Claridge TD, Schofield CJ (July 2012). "Development and application of a fluoride-detection-based fluorescence assay for γ-butyrobetaine hydroxylase". ChemBioChem. 13 (11): 1559–1563. doi:10.1002/cbic.201200256. PMID 22730246. S2CID 13956474.
  51. ^ Flashman, Emily; Bagg, Eleanor A. L.; Chowdhury, Rasheduzzaman; Mecinović, Jasmin; Loenarz, Christoph; McDonough, Michael A.; Hewitson, Kirsty S.; Schofield, Christopher J. (15 February 2008). "Kinetic Rationale for Selectivity toward N- and C-terminal Oxygen-dependent Degradation Domain Substrates Mediated by a Loop Region of Hypoxia-Inducible Factor Prolyl Hydroxylases". Journal of Biological Chemistry. 283 (7): 3808–3815. doi:10.1074/jbc.M707411200. ISSN 0021-9258. PMID 18063574.
  52. ^ Demetriades M, Leung IK, Chowdhury R, Chan MC, McDonough MA, Yeoh KK, Tian YM, Claridge TD, Ratcliffe PJ, Woon EC, Schofield CJ (July 2012). "Dynamic combinatorial chemistry employing boronic acids/boronate esters leads to potent oxygenase inhibitors". Angew. Chem. Int. Ed. 51 (27): 6672–6675. doi:10.1002/anie.201202000. PMID 22639232.
  53. ^ Leung IK, Brown T Jr, Schofield CJ, Claridge TD (March 2011). "An approach to enzyme inhibition employing reversible boronate ester formation". Med. Chem. Commun. 2 (5): 390–395. doi:10.1039/C1MD00011J.
  54. ^ Chan, Mun Chiang; Atasoylu, Onur; Hodson, Emma; Tumber, Anthony; Leung, Ivanhoe K. H.; Chowdhury, Rasheduzzaman; Gómez-Pérez, Verónica; Demetriades, Marina; Rydzik, Anna M. (6 July 2015). "Potent and Selective Triazole-Based Inhibitors of the Hypoxia-Inducible Factor Prolyl-Hydroxylases with Activity in the Murine Brain". PLOS ONE. 10 (7): e0132004. Bibcode:2015PLoSO..1032004C. doi:10.1371/journal.pone.0132004. ISSN 1932-6203. PMC 4492579. PMID 26147748.
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  56. ^ van Berkel, Sander S.; Nettleship, Joanne E.; Leung, Ivanhoe K. H.; Brem, Jürgen; Choi, Hwanho; Stuart, David I.; Claridge, Timothy D. W.; McDonough, Michael A.; Owens, Raymond J. (15 August 2013). "Binding of (5 S )-Penicilloic Acid to Penicillin Binding Protein 3". ACS Chemical Biology. 8 (10): 2112–2116. doi:10.1021/cb400200h. PMID 23899657.
  57. ^ MacKenzie, Alasdair K.; Kershaw, Nadia J.; Hernandez, Helena; Robinson, Carol V.; Schofield, Christopher J.; Andersson, Inger (19 January 2007). "Clavulanic Acid Dehydrogenase: Structural and Biochemical Analysis of the Final Step in the Biosynthesis of the β-Lactamase Inhibitor Clavulanic Acid † , ‡". Biochemistry. 46 (6): 1523–1533. doi:10.1021/bi061978x. PMID 17279617.
  58. ^ a b Borowski, Tomasz; Broclawik, Ewa; Schofield, Christopher J.; Siegbahn, Per E. M. (30 April 2006). "Epimerization and desaturation by carbapenem synthase (CarC). A hybrid DFT study". Journal of Computational Chemistry. 27 (6): 740–748. doi:10.1002/jcc.20384. ISSN 1096-987X. PMID 16521121. S2CID 21775977.
  59. ^ Mackenzie, Alasdair K.; Valegård, Karin; Iqbal, Aman; Caines, Matthew E. C.; Kershaw, Nadia J.; Jensen, Susan E.; Schofield, Christopher J.; Andersson, Inger (19 February 2010). "Crystal Structures of an Oligopeptide-Binding Protein from the Biosynthetic Pathway of the β-Lactamase Inhibitor Clavulanic Acid". Journal of Molecular Biology. 396 (2): 332–344. doi:10.1016/j.jmb.2009.11.045. PMID 19941870.
  60. ^ Long, Alexandra J.; Clifton, Ian J.; Roach, Peter L.; Baldwin, Jack E.; Schofield, Christopher J.; Rutledge, Peter J. (15 June 2003). "Structural studies on the reaction of isopenicillin N synthase with the substrate analogue delta-(l-alpha-aminoadipoyl)-l-cysteinyl-d-alpha-aminobutyrate". Biochemical Journal. 372 (3): 687–693. doi:10.1042/bj20021627. ISSN 0264-6021. PMC 1223433. PMID 12622704.
  61. ^ Sleeman, Mark C; MacKinnon, Colin H; Hewitson, Kirsty S; Schofield, Christopher J (25 February 2002). "Enzymatic Synthesis of Monocyclic β-Lactams". Bioorganic & Medicinal Chemistry Letters. 12 (4): 597–599. doi:10.1016/S0960-894X(01)00806-X. PMID 11844680.
  62. ^ Liénard, Benoît M. R.; Hüting, Rebekka; Lassaux, Patricia; Galleni, Moreno; Frère, Jean-Marie; Schofield, Christopher J. (19 January 2008). "Dynamic Combinatorial Mass Spectrometry Leads to Metallo-β-lactamase Inhibitors". Journal of Medicinal Chemistry. 51 (3): 684–688. doi:10.1021/jm070866g. PMID 18205296.
  63. ^ Brem, Jürgen; Berkel, Sander S. van; Zollman, David; Lee, Sook Y.; Gileadi, Opher; McHugh, Peter J.; Walsh, Timothy R.; McDonough, Michael A.; Schofield, Christopher J. (1 January 2016). "Structural Basis of Metallo-β-Lactamase Inhibition by Captopril Stereoisomers". Antimicrobial Agents and Chemotherapy. 60 (1): 142–150. doi:10.1128/AAC.01335-15. ISSN 0066-4804. PMC 4704194. PMID 26482303.
  64. ^ Liénard, Benoît M. R.; Horsfall, Louise E.; Galleni, Moreno; Frère, Jean-Marie; Schofield, Christopher J. (15 February 2007). "Inhibitors of the FEZ-1 metallo-β-lactamase". Bioorganic & Medicinal Chemistry Letters. 17 (4): 964–968. doi:10.1016/j.bmcl.2006.11.053. PMID 17157014.
  65. ^ Brem, Jürgen; Cain, Ricky; Cahill, Samuel; McDonough, Michael A.; Clifton, Ian J.; Jiménez-Castellanos, Juan-Carlos; Avison, Matthew B.; Spencer, James; Fishwick, Colin W. G. (8 August 2016). "Structural basis of metallo-β-lactamase, serine-β-lactamase and penicillin-binding protein inhibition by cyclic boronates". Nature Communications. 7: 12406. Bibcode:2016NatCo...712406B. doi:10.1038/ncomms12406. PMC 4979060. PMID 27499424.
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  71. ^ "Jeremy Knowles Award 2011 Winner". rsc.org. Retrieved 25 February 2017.
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