Christopher J. Schofield

Christopher J. Schofield
Born Christopher Joseph Schofield
June, 17
United Kingdom
Other names Chris Schofield, CJS
Nationality British
Fields Hypoxic Response, Epigenetic, Oxygenases, Antibiotic Resistance
Institutions Chemistry Research Laboratory, University of Oxford
Alma mater

University of Manchester (BSc)

University of Oxford (DPhil)
Notable awards Fellow of the Royal Society

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 the Head of Organic 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] Prof Schofield is an international leader in functional, structural and mechanistic understanding of enzymes that employ oxygen and 2-oxoglutarate co-substrates.[4] His work has opened up new fields in antibiotic research,[5] oxygen sensing,[6] and gene regulation.[7]

After groundbreaking work on plant and microbial oxygenases,[4] he pioneered structurally informed functional assignments for 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 that are being pursued by numerous academic and commercial laboratories.[12]

Education

Chris Schofield 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,[13] and in 2011 he was appointed the Head of Organic Chemistry[14] at the Department of Chemistry, University of Oxford. In 2013, he was elected a Fellow of the Royal Society, FRS.[15]

Research

Chris Schofield runs a laboratory of undergraduate Part-II, Master, and DPhil students, visiting researchers, post-doctoral research assistants, and staff members. His laboratory members have received scholarships and funding from the British Heart Foundation, the BBSRC, the Wellcome Trust, the Biochemical Society, Cancer Research UK, and other funding bodies. The work in the laboratory 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[16] that mediates the cellular response to oxygen availability in multicellular organisms,[6][17] ranging from the simplest known animal Trichoplax adhaerens to humans.[4][6][18][19][20] Investigating the structures and mechanisms of the HIF prolyl hydroxylases is a current focus of the work.[10][21] The group solved crystal structures of PHD2[9][22] - one of the human prolyl hydroxylases and discovered that the HIF asparaginyl hydroxylase also catalyses hydroxylation of conserved motifs,[23] 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][24] – in collaboration with the Structural Genomics Consortium. The histone demethylases[25][26] are of interest both with respect to their links to diseases, including cancer[27][28] and inflammatory diseases,[29] as well as the role of methylation in transcriptional regulation.[30] Recent areas of interest include the fat mass and obesity protein[31][32] which was shown to be a nucleic acid demethylase[33] and JMJD6[34][35] 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,[36] most of which use the Krebs cycle intermediate, 2-oxoglutarate (2OG), as a cosubstrate.[37] The group are interested in understanding these enzymes[38] 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.[39] The research focuses on members of the family that are linked to disease, or can be targeted for the treatment of disease.[40][41] Techniques involved in this interdisciplinary research include proteomics,[42] X-ray crystallography,[43] biological mass spectrometry,[44][44] molecular biology,[45] enzyme kinetics[46] and organic synthesis/medicinal chemistry.[47][48]

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,[49] cephalosporin, clavam,[50] and carbapenem[51] antibiotics. The group's biosynthetic work has focused on the clavams[52] and carbapenems,[51] with a particular focus being on the mechanism and structures of enzymes that catalyse chemically 'interesting' steps.[53][54] The biggest threat to the continued use of β-lactam antibiotics is that of bacterial resistance. Prof Schofield is currently working on the design and synthesis of enzyme inhibitors[55][56][57][58] for the metallo β-lactamases[59] – there are no clinically used inhibitor[60] of these enzymes but they pose a significant threat as they catalyse the hydrolysis of almost all clinically used β-lactam antibiotics.[61] A particular interest involves human metallo β-lactamases which share the same fold[62]

Awards and Honours

Prof Schofield was elected a Fellow of the Royal Society in 2013.[15]

References

  1. ↑ "Professor C.J. Schofield". research.chem.ox.ac.uk. Retrieved 2016-08-08.
  2. 1 2 "Home - Schofield Group". schofield.chem.ox.ac.uk. Retrieved 2016-08-08.
  3. 1 2 "Professor Chris Schofield FRS | Hertford College". www.hertford.ox.ac.uk. Retrieved 2016-08-08.
  4. 1 2 3 Chowdhury, Rasheduzzaman; Sekirnik, Rok; Brissett, Nigel C.; Krojer, Tobias; Ho, Chia-hua; Ng, Stanley S.; Clifton, Ian J.; Ge, Wei; Kershaw, Nadia J. (2014-06-19). "Ribosomal oxygenases are structurally conserved from prokaryotes to humans". Nature. 510 (7505): 422–426. doi:10.1038/nature13263. ISSN 0028-0836. PMC 4066111Freely accessible. PMID 24814345.
  5. 1 2 Hamed, Refaat B.; Gomez-Castellanos, J. Ruben; Henry, Luc; Ducho, Christian; McDonough, Michael A.; Schofield, Christopher J. (2012-12-10). "The enzymes of β-lactam biosynthesis". Natural Product Reports. 30 (1). doi:10.1039/C2NP20065A. ISSN 1460-4752.
  6. 1 2 3 Schofield, Christopher J.; Ratcliffe, Peter J. (2004-05-01). "Oxygen sensing by HIF hydroxylases". Nature Reviews Molecular Cell Biology. 5 (5): 343–354. doi:10.1038/nrm1366. ISSN 1471-0072.
  7. 1 2 Thinnes, Cyrille C.; England, Katherine S.; Kawamura, Akane; Chowdhury, Rasheduzzaman; Schofield, Christopher J.; Hopkinson, Richard J. (2014-12-01). "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 4316176Freely accessible. PMID 24859458.
  8. 1 2 Horita, Shoichiro; Scotti, John S.; Thinnes, Cyrille; Mottaghi-Taromsari, Yousef S.; Thalhammer, Armin; Ge, Wei; Aik, WeiShen; Loenarz, Christoph; Schofield, Christopher J. (2015-04-07). "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 4396695Freely accessible. PMID 25728928.
  9. 1 2 "Structural Basis for Binding of Hypoxia-Inducible Factor to the Oxygen-Sensing Prolyl Hydroxylases".
  10. 1 2 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. (2002-06-27). "Structural basis for the recognition of hydroxyproline in HIF-1α by pVHL". Nature. 417 (6892): 975–978. doi:10.1038/nature00767. ISSN 0028-0836.
  11. 1 2 Webby, Celia J.; Wolf, Alexander; Gromak, Natalia; Dreger, Mathias; Kramer, Holger; Kessler, Benedikt; Nielsen, Michael L.; Schmitz, Corinna; Butler, Danica S. (2009-07-03). "Jmjd6 Catalyses Lysyl-Hydroxylation of U2AF65, a Protein Associated with RNA Splicing". Science. 325 (5936): 90–93. doi:10.1126/science.1175865. ISSN 0036-8075. PMID 19574390.
  12. ↑ "ReOx Ltd - Oxford Spin-out to Develop New Drug Therapies". Retrieved 2016-08-08.
  13. ↑ "Professor C.J. Schofield". research.chem.ox.ac.uk. Retrieved 2016-08-08.
  14. ↑ "SELECTBIO - Epigenetics Speaker Biography". SELECTBIO. Retrieved 2016-08-08.
  15. 1 2 "Christopher Schofield". royalsociety.org. Retrieved 2016-08-08.
  16. ↑ Wilkins, Sarah E.; Abboud, Martine I.; Hancock, Rebecca L.; Schofield, Christopher J. (2016-04-19). "Targeting Protein–Protein Interactions in the HIF System". ChemMedChem. 11 (8): 773–786. doi:10.1002/cmdc.201600012. ISSN 1860-7187. PMC 4848768Freely accessible. PMID 26997519.
  17. ↑ Jaakkola, Panu; Mole, David R.; Tian, Ya-Min; Wilson, Michael I.; Gielbert, Janine; Gaskell, Simon J.; Kriegsheim, Alexander von; Hebestreit, Holger F.; Mukherji, Mridul (2001-04-20). "Targeting of HIF-α to the von Hippel-Lindau Ubiquitylation Complex by O2-Regulated Prolyl Hydroxylation". Science. 292 (5516): 468–472. doi:10.1126/science.1059796. ISSN 0036-8075. PMID 11292861.
  18. ↑ 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. (2001-10-05). "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.
  19. ↑ Ge, Wei; Wolf, Alexander; Feng, Tianshu; Ho, Chia-hua; Sekirnik, Rok; Zayer, Adam; Granatino, Nicolas; Cockman, Matthew E.; Loenarz, Christoph (2012-12-01). "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 4972389Freely accessible. PMID 23103944.
  20. ↑ 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. (2011-04-15). "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 3075650Freely accessible. PMID 21335549.
  21. ↑ Loenarz, Christoph; Schofield, Christopher J. (2008-03-01). "Expanding chemical biology of 2-oxoglutarate oxygenases". Nature Chemical Biology. 4 (3): 152–156. doi:10.1038/nchembio0308-152. ISSN 1552-4450.
  22. ↑ McDonough, Michael A.; Li, Vivian; Flashman, Emily; Chowdhury, Rasheduzzaman; Mohr, Christopher; Liénard, Benoît M. R.; Zondlo, James; Oldham, Neil J.; Clifton, Ian J. (2006-06-27). "Cellular oxygen sensing: Crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2)". Proceedings of the National Academy of Sciences. 103 (26): 9814–9819. doi:10.1073/pnas.0601283103. ISSN 0027-8424. PMC 1502536Freely accessible. PMID 16782814.
  23. ↑ 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. (2011-04-01). "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 3569879Freely accessible. PMID 21251231.
  24. ↑ Langley, Gareth W.; Brinkø, Anne; Münzel, Martin; Walport, Louise J.; Schofield, Christopher J.; Hopkinson, Richard J. (2015-11-25). "Analysis of JmjC Demethylase-Catalyzed Demethylation Using Geometrically-Constrained Lysine Analogues". ACS Chemical Biology. 11 (3): 755–762. doi:10.1021/acschembio.5b00738.
  25. ↑ Walport, Louise J.; Hopkinson, Richard J.; Chowdhury, Rasheduzzaman; Schiller, Rachel; Ge, Wei; Kawamura, Akane; Schofield, Christopher J. (2016-06-23). "Arginine demethylation is catalysed by a subset of JmjC histone lysine demethylases". Nature Communications. 7: 11974. doi:10.1038/ncomms11974. PMC 4931022Freely accessible. PMID 27337104.
  26. ↑ 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 (2007-07-05). "Crystal structures of histone demethylase JMJD2A reveal basis for substrate specificity". Nature. 448 (7149): 87–91. doi:10.1038/nature05971. ISSN 0028-0836.
  27. ↑ Kawamura, Akane; Loenarz, Christoph; Schofield, Christopher J. (2011-09-01). "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.
  28. ↑ Rotili, Dante; Tomassi, Stefano; Conte, Mariarosaria; Benedetti, Rosaria; Tortorici, Marcello; Ciossani, Giuseppe; Valente, Sergio; Marrocco, Biagina; Labella, Donatella (2013-12-19). "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.
  29. ↑ Kruidenier, Laurens; Chung, Chun-wa; Cheng, Zhongjun; Liddle, John; Che, KaHing; Joberty, Gerard; Bantscheff, Marcus; Bountra, Chas; Bridges, Angela (2012-08-16). "A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response". Nature. 488 (7411): 404–408. doi:10.1038/nature11262. ISSN 0028-0836. PMC 4691848Freely accessible. PMID 22842901.
  30. ↑ Lercher, Lukas; McDonough, Michael A.; El-Sagheer, Afaf H.; Thalhammer, Armin; Kriaucionis, Skirmantas; Brown, Tom; Schofield, Christopher J. (2014-01-23). "Structural insights into how 5-hydroxymethylation influences transcription factor binding". Chemical Communications. 50 (15). doi:10.1039/C3CC48151D. ISSN 1364-548X.
  31. ↑ Church, Chris; Lee, Sheena; Bagg, Eleanor A. L.; McTaggart, James S.; Deacon, Robert; Gerken, Thomas; Lee, Angela; Moir, Lee; Mecinović, Jasmin (2009-08-14). "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.
  32. ↑ 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. (2013-04-23). "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.
  33. ↑ 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 (2007-11-30). "The Obesity-Associated FTO Gene Encodes a 2-Oxoglutarate-Dependent Nucleic Acid Demethylase". Science. 318 (5855): 1469–1472. doi:10.1126/science.1151710. ISSN 0036-8075. PMC 2668859Freely accessible. PMID 17991826.
  34. ↑ Church, Chris; Lee, Sheena; Bagg, Eleanor A. L.; McTaggart, James S.; Deacon, Robert; Gerken, Thomas; Lee, Angela; Moir, Lee; Mecinović, Jasmin (2009-08-14). "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 2719869Freely accessible. PMID 19680540.
  35. ↑ Mantri, Monica; Krojer, Tobias; Bagg, Eleanor A.; Webby, Celia J.; Butler, Danica S.; Kochan, Grazyna; Kavanagh, Kathryn L.; Oppermann, Udo; McDonough, Michael A. (2010-08-13). "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.
  36. ↑ Clifton, Ian J.; McDonough, Michael A.; Ehrismann, Dominic; Kershaw, Nadia J.; Granatino, Nicolas; Schofield, Christopher J. (2006-04-01). "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.
  37. ↑ Welford, Richard W.D.; Kirkpatrick, Joanna M.; McNeill, Luke A.; Puri, Munish; Oldham, Neil J.; Schofield, Christopher J. (2005-12-05). "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): 6688–6688. doi:10.1016/j.febslet.2005.11.001. ISSN 1873-3468.
  38. ↑ Loenarz, Christoph; Mecinović, Jasmin; Chowdhury, Rasheduzzaman; McNeill, LukeA.; Flashman, Emily; Schofield, ChristopherJ. (2009-02-23). "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.
  39. ↑ Astuti, Dewi; Ricketts, Christopher J.; Chowdhury, Rasheduzzaman; McDonough, Michael A.; Gentle, Dean; Kirby, Gail; Schlisio, Susanne; Kenchappa, Rajappa S.; Carter, Bruce D. (2011-02-01). "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 3006001Freely accessible. PMID 20959442.
  40. ↑ Rose, Nathan R.; McDonough, Michael A.; King, Oliver N. F.; Kawamura, Akane; Schofield, Christopher J. (2011-07-14). "Inhibition of 2-oxoglutarate dependent oxygenases". Chemical Society Reviews. 40 (8). doi:10.1039/C0CS00203H. ISSN 1460-4744.
  41. ↑ Aik, WeiShen; Scotti, John S.; Choi, Hwanho; Gong, Lingzhi; Demetriades, Marina; Schofield, Christopher J.; McDonough, Michael A. (2014-04-01). "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 3985658Freely accessible. PMID 24489119.
  42. ↑ Mackeen, Mukram M.; Kramer, Holger B.; Chang, Kai-Hsuan; Coleman, Matthew L.; Hopkinson, Richard J.; Schofield, Christopher J.; Kessler, Benedikt M. (2010-07-21). "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 4681095Freely accessible. PMID 20583823.
  43. ↑ Clifton, Ian J.; Hsueh, Li-Ching; Baldwin, Jack E.; Harlos, Karl; Schofield, Christopher J. (2001-12-15). "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.
  44. 1 2 Mecinović, Jasmin; Chowdhury, Rasheduzzaman; Flashman, Emily; Schofield, Christopher J. (2009-10-15). "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.
  45. ↑ Tan, SuatCheng; Carr, CarolynA.; Yeoh, KarKheng; Schofield, ChristopherJ.; Davies, KayE.; Clarke, Kieran (2012-04-01). "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 3294216Freely accessible. PMID 22065248.
  46. ↑ Flashman, Emily; Bagg, Eleanor A. L.; Chowdhury, Rasheduzzaman; Mecinović, Jasmin; Loenarz, Christoph; McDonough, Michael A.; Hewitson, Kirsty S.; Schofield, Christopher J. (2008-02-15). "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.
  47. ↑ Chan, Mun Chiang; Atasoylu, Onur; Hodson, Emma; Tumber, Anthony; Leung, Ivanhoe K. H.; Chowdhury, Rasheduzzaman; Gómez-Pérez, Verónica; Demetriades, Marina; Rydzik, Anna M. (2015-07-06). "Potent and Selective Triazole-Based Inhibitors of the Hypoxia-Inducible Factor Prolyl-Hydroxylases with Activity in the Murine Brain". PLOS ONE. 10 (7): e0132004. doi:10.1371/journal.pone.0132004. ISSN 1932-6203. PMC 4492579Freely accessible. PMID 26147748.
  48. ↑ Thinnes, C. C.; Tumber, A.; Yapp, C.; Scozzafava, G.; Yeh, T.; Chan, M. C.; Tran, T. A.; Hsu, K.; Tarhonskaya, H. (2015-10-08). "Betti reaction enables efficient synthesis of 8-hydroxyquinoline inhibitors of 2-oxoglutarate oxygenases". Chemical Communications. 51 (84). doi:10.1039/C5CC06095H. ISSN 1364-548X.
  49. ↑ 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. (2013-08-15). "Binding of (5 S )-Penicilloic Acid to Penicillin Binding Protein 3". ACS Chemical Biology. 8 (10): 2112–2116. doi:10.1021/cb400200h.
  50. ↑ MacKenzie, Alasdair K.; Kershaw, Nadia J.; Hernandez, Helena; Robinson, Carol V.; Schofield, Christopher J.; Andersson, Inger (2007-01-19). "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.
  51. 1 2 Borowski, Tomasz; Broclawik, Ewa; Schofield, Christopher J.; Siegbahn, Per E. M. (2006-04-30). "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.
  52. ↑ Mackenzie, Alasdair K.; Valegård, Karin; Iqbal, Aman; Caines, Matthew E. C.; Kershaw, Nadia J.; Jensen, Susan E.; Schofield, Christopher J.; Andersson, Inger (2010-02-19). "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.
  53. ↑ Long, Alexandra J.; Clifton, Ian J.; Roach, Peter L.; Baldwin, Jack E.; Schofield, Christopher J.; Rutledge, Peter J. (2003-06-15). "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. PMID 12622704.
  54. ↑ Sleeman, Mark C; MacKinnon, Colin H; Hewitson, Kirsty S; Schofield, Christopher J (2002-02-25). "Enzymatic Synthesis of Monocyclic β-Lactams". Bioorganic & Medicinal Chemistry Letters. 12 (4): 597–599. doi:10.1016/S0960-894X(01)00806-X.
  55. ↑ Liénard, Benoît M. R.; Hüting, Rebekka; Lassaux, Patricia; Galleni, Moreno; Frère, Jean-Marie; Schofield, Christopher J. (2008-01-19). "Dynamic Combinatorial Mass Spectrometry Leads to Metallo-β-lactamase Inhibitors". Journal of Medicinal Chemistry. 51 (3): 684–688. doi:10.1021/jm070866g.
  56. ↑ 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. (2016-01-01). "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 4704194Freely accessible. PMID 26482303.
  57. ↑ Liénard, Benoît M. R.; Horsfall, Louise E.; Galleni, Moreno; Frère, Jean-Marie; Schofield, Christopher J. (2007-02-15). "Inhibitors of the FEZ-1 metallo-β-lactamase". Bioorganic & Medicinal Chemistry Letters. 17 (4): 964–968. doi:10.1016/j.bmcl.2006.11.053.
  58. ↑ 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. (2016-08-08). "Structural basis of metallo-β-lactamase, serine-β-lactamase and penicillin-binding protein inhibition by cyclic boronates". Nature Communications. 7: 12406. doi:10.1038/ncomms12406.
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