Christopher J. Schofield Explained

Christopher J. Schofield
Birth Name:Christopher Joseph Schofield
Birth Date:1960 6, df=yes
Birth Place:United Kingdom
Other Names:Chris Schofield, CJS
Nationality:British
Fields:Hypoxic Response, Epigenetic, Oxygenases, Antibiotic Resistance
Workplaces:Chemistry Research Laboratory, University of Oxford
Alma Mater:University of Manchester (BSc)University of Oxford (DPhil)
Awards:Fellow of the Royal Society
Website:http://schofield.chem.ox.ac.uk/homehttp://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, 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

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 and a Fellow of Hertford College 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

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

Molecular Mechanisms of the Hypoxic Response

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,[16] ranging from the simplest known animal Trichoplax adhaerens to humans.[6] [17] [18] [19] Investigating the structures and mechanisms of the HIF prolyl hydroxylases is a current focus of the work.[20] The group solved crystal structures of PHD2[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

A current focus of the group is modification of histones, in particular oxygenase catalysed N-demethylation of histone methylated-lysine residues[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.

Structural and Functional Studies on 2OG Oxygenases

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, 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

Most clinically used antibiotics are based upon natural products. 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

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

2013: Fellow of the Royal Society (London); 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)

External links

Notes and References

  1. Web site: Christopher Schofield. University of Oxford. 2023-07-24.
  2. Web site: Home – Schofield Group. University of Oxford. 2016-08-08.
  3. Web site: Professor Chris Schofield FRS Hertford College. University of Oxford. 2016-08-08.
  4. 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. en. 510. 7505. 422–426. 10.1038/nature13263. 0028-0836. 4066111. 24814345. 2014Natur.510..422C.
  5. 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. en. 30. 1. 10.1039/C2NP20065A. 1460-4752. 21–107. 23135477.
  6. Schofield. Christopher J.. Ratcliffe. Peter J.. 1 May 2004. Oxygen sensing by HIF hydroxylases. Nature Reviews Molecular Cell Biology. en. 5. 5. 343–354. 10.1038/nrm1366. 15122348. 6586977. 1471-0072.
  7. 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. 10.1016/j.bbagrm.2014.05.009. 4316176. 24859458.
  8. 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. 10.1016/j.str.2015.01.014. 4396695. 25728928.
  9. Structural Basis for Binding of Hypoxia-Inducible Factor to the Oxygen-Sensing Prolyl Hydroxylases. 10.1016/j.str.2009.06.002 . 17. 7 . Structure. 981–989. 19604478. July 2009 . Chowdhury . R . McDonough . MA . Mecinović . J . Loenarz . C . Flashman . E . Hewitson . KS . Domene . C . Schofield . CJ. Carmen Domene. free .
  10. 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. en. 417. 6892. 975–978. 10.1038/nature00767. 0028-0836. 12050673. 2002Natur.417..975H. 4388644.
  11. 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. en. 325. 5936. 90–93. 10.1126/science.1175865. 0036-8075. 19574390. 2009Sci...325...90W. 10033/78493. 38938528. free.
  12. Web site: ReOx Ltd - Oxford Spin-out to Develop New Drug Therapies. 2016-08-08.
  13. Web site: SELECTBIO – Epigenetics Speaker Biography. SELECTBIO. 2016-08-08.
  14. Web site: Christopher Schofield. royalsociety.org. 2016-08-08.
  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. en. 11. 8. 773–786. 10.1002/cmdc.201600012. 1860-7187. 4848768. 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. en. 292. 5516. 468–472. 10.1126/science.1059796. 0036-8075. 11292861. 2001Sci...292..468J. 20914281. free.
  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. 10.1016/S0092-8674(01)00507-4. 11595184. free.
  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. en. 8. 12. 960–962. 10.1038/nchembio.1093. 1552-4450. 4972389. 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. en. 286. 15. 13041–13051. 10.1074/jbc.M110.211110. 0021-9258. 3075650. 21335549. free.
  20. Loenarz. Christoph. Schofield. Christopher J.. 1 March 2008. Expanding chemical biology of 2-oxoglutarate oxygenases. Nature Chemical Biology. en. 4. 3. 152–156. 10.1038/nchembio0308-152. 1552-4450. 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. en. 103. 26. 9814–9819. 10.1073/pnas.0601283103. 0027-8424. 1502536. 16782814. 2006PNAS..103.9814M. free.
  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. en. 278. 7. 1086–1097. 10.1111/j.1742-4658.2011.08022.x. 1742-4658. 3569879. 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. EN. 11. 3. 755–762. 10.1021/acschembio.5b00738. 26555343. 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. en. 7. 11974. 10.1038/ncomms11974. 4931022. 27337104. 2016NatCo...711974W.
  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. en. 448. 7149. 87–91. 10.1038/nature05971. 0028-0836. 17589501. 2007Natur.448...87N. 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. 10.4161/cc.10.17.16745. 1538-4101. 21857150. free.
  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. EN. 57. 1. 42–55. 10.1021/jm4012802. 24325601. 11573/542432 .
  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. en. 488. 7411. 404–408. 10.1038/nature11262. 0028-0836. 4691848. 22842901. 2012Natur.488..404K.
  29. Lercher. Lukas. McDonough. Michael A.. El-Sagheer. Afaf H.. Thalhammer. Armin. Kriaucionis. Skirmantas. Brown. Tom. Schofield. Christopher J.. 6489226. 23 January 2014. Structural insights into how 5-hydroxymethylation influences transcription factor binding. Chemical Communications. en. 50. 15. 10.1039/C3CC48151D. 24287551. 1364-548X. 1794–1796.
  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. 10.1371/journal.pgen.1000599. 1553-7404. 19680540. 2719869 . free .
  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. EN. 56. 9. 3680–3688. 10.1021/jm400193d. 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. en. 318. 5855. 1469–1472. 10.1126/science.1151710. 0036-8075. 2668859. 17991826. 2007Sci...318.1469G.
  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. 10.1371/journal.pgen.1000599. 1553-7404. 2719869. 19680540 . free .
  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. 10.1016/j.jmb.2010.05.054. 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. 10.1016/j.jinorgbio.2006.01.024. 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. en. 579. 29. 6688. 10.1016/j.febslet.2005.11.001. 1873-3468. free. 10536/DRO/DU:30095401. free.
  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. en. 48. 10. 1784–1787. 10.1002/anie.200805427. 1521-3773. 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. en. 18. 1. 73–83. 10.1677/ERC-10-0113. 1351-0088. 3006001. 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. en. 40. 8. 10.1039/C0CS00203H. 1460-4744. 4364–97. 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. en. 42. 7. 4741–4754. 10.1093/nar/gku085. 0305-1048. 3985658. 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. EN. 9. 8. 4082–4092. 10.1021/pr100269b. 4681095. 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. en. 268. 24. 6625–6636. 10.1046/j.0014-2956.2001.02617.x. 1432-1033. 11737217. free.
  43. Mbenza NM, Vadakkedath PG, McGillivray DJ, Leung IK . NMR studies of the non-haem Fe(II) and 2-oxoglutarate-dependent oxygenases . J. Inorg. Biochem. . 177 . 384–394 . December 2017 . 28893416 . 10.1016/j.jinorgbio.2017.08.032 .
  44. Khan A, Leśniak RK, Brem J, Rydzik AM, Choi H, Leung IK, McDonough MA, Schofield CJ, Claridge TD . Development and application of ligand-based NMR screening assays for γ-butyrobetaine hydroxylase . Med. Chem. Commun. . 7 . 5 . 873–880 . February 2016 . 10.1039/C6MD00004E . free . 2292/30083 . free .
  45. Leung IK, Demetriades M, Hardy AP, Lejeune C, Smart TJ, Szöllössi A, Kawamura A, Schofield CJ, Claridge TD . Reporter ligand NMR screening method for 2-oxoglutarate oxygenase inhibitors . J. Med. Chem. . 56 . 2 . 547–555 . January 2013 . 23234607 . 10.1021/jm301583m . 4673903.
  46. Leung IK, Flashman E, Yeoh KK, Schofield CJ, Claridge TD . Using NMR solvent water relaxation to investigate metalloenzyme-ligand binding interactions . J. Med. Chem. . 53 . 2 . 867–875 . January 2010 . 20025281 . 10.1021/jm901537q .
  47. Rydzik AM, Leung IK, Thalhammer A, Kochan GT, Claridge TD, Schofield CJ . Fluoromethylated derivatives of carnitine biosynthesis intermediates - synthesis and applications . Chem. Commun. . 50 . 10 . 1175–1177 . February 2014 . 24317009 . 10.1039/c3cc47581f . free .
  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. 10.1016/j.ab.2009.06.029. 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. 10.1007/s11033-011-1281-5. 0301-4851. 3294216. 22065248.
  50. Rydzik AM, Leung IK, Kochan GT, Thalhammer A, Oppermann U, Claridge TD, Schofield CJ . Development and application of a fluoride-detection-based fluorescence assay for γ-butyrobetaine hydroxylase . ChemBioChem . 13 . 11 . 1559–1563 . July 2012 . 22730246 . 10.1002/cbic.201200256 . 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. en. 283. 7. 3808–3815. 10.1074/jbc.M707411200. 0021-9258. 18063574. free.
  52. Demetriades M, Leung IK, Chowdhury R, Chan MC, McDonough MA, Yeoh KK, Tian YM, Claridge TD, Ratcliffe PJ, Woon EC, Schofield CJ . Dynamic combinatorial chemistry employing boronic acids/boronate esters leads to potent oxygenase inhibitors . Angew. Chem. Int. Ed. . 51 . 27 . 6672–6675 . July 2012 . 22639232 . 10.1002/anie.201202000 .
  53. Leung IK, Brown T Jr, Schofield CJ, Claridge TD . An approach to enzyme inhibition employing reversible boronate ester formation . Med. Chem. Commun. . 2 . 5 . 390–395 . March 2011 . 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. 10.1371/journal.pone.0132004. 1932-6203. 4492579. 26147748. 2015PLoSO..1032004C. free.
  55. Thinnes. C. C.. Tumber. A.. Yapp. C.. Scozzafava. G.. Yeh. T.. Chan. M. C.. Tran. T. A.. Hsu. K.. Tarhonskaya. H.. 8 October 2015. Betti reaction enables efficient synthesis of 8-hydroxyquinoline inhibitors of 2-oxoglutarate oxygenases. Chemical Communications. en. 51. 84. 10.1039/C5CC06095H. 26345662. 1364-548X. 15458–15461.
  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. EN. 8. 10. 2112–2116. 10.1021/cb400200h. 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. en. 46. 6. 1523–1533. 10.1021/bi061978x. 17279617.
  58. 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. en. 27. 6. 740–748. 10.1002/jcc.20384. 16521121. 21775977. 1096-987X. free.
  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. 10.1016/j.jmb.2009.11.045. 19941870.
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  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. en. 60. 1. 142–150. 10.1128/AAC.01335-15. 0066-4804. 4704194. 26482303.
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  69. Pettinati. Ilaria. Brem. Jürgen. McDonough. Michael A.. Schofield. Christopher J.. 1 May 2015. Crystal structure of human persulfide dioxygenase: structural basis of ethylmalonic encephalopathy. Human Molecular Genetics. en. 24. 9. 2458–2469. 10.1093/hmg/ddv007. 0964-6906. 4383860. 25596185.
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