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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 63)
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
Website http://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

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

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, [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

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

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

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

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

  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.
  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. 51 (84): 15458–15461. doi: 10.1039/C5CC06095H. ISSN  1364-548X. PMID  26345662.
  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.
  66. ^ Makena, Anne; Düzgün, Azer Ö; Brem, Jürgen; McDonough, Michael A.; Rydzik, Anna M.; Abboud, Martine I.; Saral, Ayşegül; Çiçek, Ayşegül Ç; Sandalli, Cemal (1 March 2016). "Comparison of Verona Integron-Borne Metallo-β-Lactamase (VIM) Variants Reveals Differences in Stability and Inhibition Profiles". Antimicrobial Agents and Chemotherapy. 60 (3): 1377–1384. doi: 10.1128/AAC.01768-15. ISSN  0066-4804. PMC  4775916. PMID  26666919.
  67. ^ Abboud, Martine I.; Damblon, Christian; Brem, Jürgen; Smargiasso, Nicolas; Mercuri, Paola; Gilbert, Bernard; Rydzik, Anna M.; Claridge, Timothy D. W.; Schofield, Christopher J. (11 July 2016). "Interaction of Avibactam with Class B Metallo-β-lactamases". Antimicrobial Agents and Chemotherapy. 60 (10): AAC.00897–16. doi: 10.1128/AAC.00897-16. ISSN  0066-4804. PMC  5038302. PMID  27401561.
  68. ^ Makena, Anne; Brem, Jürgen; Pfeffer, Inga; Geffen, Rebecca E. J.; Wilkins, Sarah E.; Tarhonskaya, Hanna; Flashman, Emily; Phee, Lynette M.; Wareham, David W. (1 February 2015). "Biochemical characterization of New Delhi metallo-β-lactamase variants reveals differences in protein stability". Journal of Antimicrobial Chemotherapy. 70 (2): 463–469. doi: 10.1093/jac/dku403. ISSN  0305-7453. PMC  4291237. PMID  25324420.
  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. 24 (9): 2458–2469. doi: 10.1093/hmg/ddv007. ISSN  0964-6906. PMC  4383860. PMID  25596185.
  70. ^ Council, Biotechnology and Biological Sciences Research. "Research Advisory Panel – BBSRC". bbsrc.ac.uk. Retrieved 25 February 2017.
  71. ^ "Jeremy Knowles Award 2011 Winner". rsc.org. Retrieved 25 February 2017.

External links

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