Christopher J. Schofield
Christopher J. Schofield | |
---|---|
Born |
Christopher Joseph Schofield June, 17 1960 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 |
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 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 uncharacterized 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 honor (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 catalyzes 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 catalyzed 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 catalyze 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] biological mass spectrometry,[43][43] molecular biology,[44] enzyme kinetics,[45] and organic synthesis/medicinal chemistry.[46][47]
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,[48] cephalosporin, clavam,[49] and carbapenem[50] antibiotics. The group's biosynthetic work has focused on the clavams[51] and carbapenems,[50] with a particular focus being on the mechanism and structures of enzymes that catalyze chemically 'interesting' steps.[52][53] 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[54][55][56][57] for the metallo β-lactamases[58] – there are no clinically used inhibitor[59] of these enzymes but they pose a significant threat as they catalyze the hydrolysis of almost all clinically used β-lactam antibiotics.[60] A particular interest involves human metallo β-lactamases which share the same fold.[61]
Awards and Honors
2015-2020: Wellcome Trust Advanced Investigator Award (with Prof 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’[62]
2011: Royal Society of Chemistry, Jeremy Knowles Award, UK;[63] Highly cited paper awards (e.g. Biochemical Journal, Bioorganic and Medicinal Chemistry Letters)
2009 – 2014: PI of ERC Advanced Investigator Grant SPA GA 2008 233240 (with Prof Sir Peter Ratcliffe); Molecular Mechanism of Oxygen Sensing by Enzymes (MOOSE)
2000: Fellow of The Royal Society of Chemistry (London)
References
- 1 2 "Professor C.J. Schofield". research.chem.ox.ac.uk. Retrieved 2016-08-08.
- 1 2 "Home - Schofield Group". schofield.chem.ox.ac.uk. Retrieved 2016-08-08.
- 1 2 "Professor Chris Schofield FRS | Hertford College". www.hertford.ox.ac.uk. Retrieved 2016-08-08.
- 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. ISSN 0028-0836. PMC 4066111 . PMID 24814345. doi:10.1038/nature13263.
- 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): 21–107. ISSN 1460-4752. PMID 23135477. doi:10.1039/C2NP20065A.
- 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. ISSN 1471-0072. doi:10.1038/nrm1366.
- 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. PMC 4316176 . PMID 24859458. doi:10.1016/j.bbagrm.2014.05.009.
- 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. PMC 4396695 . PMID 25728928. doi:10.1016/j.str.2015.01.014.
- 1 2 Chowdhury, R; McDonough, MA; Mecinović, J; Loenarz, C; Flashman, E; Hewitson, KS; Domene, C; Schofield, CJ (Jul 2009). "Structural Basis for Binding of Hypoxia-Inducible Factor to the Oxygen-Sensing Prolyl Hydroxylases". Structure. 17: 981–989. PMID 19604478. doi:10.1016/j.str.2009.06.002.
- 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. ISSN 0028-0836. PMID 12050673. doi:10.1038/nature00767.
- 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. ISSN 0036-8075. PMID 19574390. doi:10.1126/science.1175865.
- ↑ "ReOx Ltd - Oxford Spin-out to Develop New Drug Therapies". Retrieved 2016-08-08.
- ↑ "SELECTBIO - Epigenetics Speaker Biography". SELECTBIO. Retrieved 2016-08-08.
- 1 2 "Christopher Schofield". royalsociety.org. Retrieved 2016-08-08.
- ↑ 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. ISSN 1860-7187. PMC 4848768 . PMID 26997519. doi:10.1002/cmdc.201600012.
- ↑ 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. ISSN 0036-8075. PMID 11292861. doi:10.1126/science.1059796.
- ↑ 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. PMID 11595184. doi:10.1016/S0092-8674(01)00507-4.
- ↑ 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. ISSN 1552-4450. PMC 4972389 . PMID 23103944. doi:10.1038/nchembio.1093.
- ↑ 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. ISSN 0021-9258. PMC 3075650 . PMID 21335549. doi:10.1074/jbc.M110.211110.
- ↑ Loenarz, Christoph; Schofield, Christopher J. (2008-03-01). "Expanding chemical biology of 2-oxoglutarate oxygenases". Nature Chemical Biology. 4 (3): 152–156. ISSN 1552-4450. PMID 18277970. doi:10.1038/nchembio0308-152.
- ↑ 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. ISSN 0027-8424. PMC 1502536 . PMID 16782814. doi:10.1073/pnas.0601283103.
- ↑ 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. ISSN 1742-4658. PMC 3569879 . PMID 21251231. doi:10.1111/j.1742-4658.2011.08022.x.
- ↑ 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.
- ↑ 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. PMC 4931022 . PMID 27337104. doi:10.1038/ncomms11974.
- ↑ 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. ISSN 0028-0836. PMID 17589501. doi:10.1038/nature05971.
- ↑ 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. ISSN 1538-4101. PMID 21857150. doi:10.4161/cc.10.17.16745.
- ↑ 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. PMID 24325601. doi:10.1021/jm4012802.
- ↑ 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. ISSN 0028-0836. PMC 4691848 . PMID 22842901. doi:10.1038/nature11262.
- ↑ 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): 1794–1796. ISSN 1364-548X. doi:10.1039/C3CC48151D.
- ↑ 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. ISSN 1553-7404. PMC 2719869 . PMID 19680540. doi:10.1371/journal.pgen.1000599.
- ↑ 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. PMID 23547775. doi:10.1021/jm400193d.
- ↑ 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. ISSN 0036-8075. PMC 2668859 . PMID 17991826. doi:10.1126/science.1151710.
- ↑ 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. ISSN 1553-7404. PMC 2719869 . PMID 19680540. doi:10.1371/journal.pgen.1000599.
- ↑ 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. PMID 20685276. doi:10.1016/j.jmb.2010.05.054.
- ↑ 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. PMID 16513174. doi:10.1016/j.jinorgbio.2006.01.024.
- ↑ 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. ISSN 1873-3468. doi:10.1016/j.febslet.2005.11.001.
- ↑ 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. ISSN 1521-3773. PMID 19180614. doi:10.1002/anie.200805427.
- ↑ 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. ISSN 1351-0088. PMC 3006001 . PMID 20959442. doi:10.1677/ERC-10-0113.
- ↑ 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): 4364–97. ISSN 1460-4744. PMID 21390379. doi:10.1039/C0CS00203H.
- ↑ 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. ISSN 0305-1048. PMC 3985658 . PMID 24489119. doi:10.1093/nar/gku085.
- ↑ 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. PMC 4681095 . PMID 20583823. doi:10.1021/pr100269b.
- ↑ 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. ISSN 1432-1033. PMID 11737217. doi:10.1046/j.0014-2956.2001.02617.x.
- 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. PMID 19563769. doi:10.1016/j.ab.2009.06.029.
- ↑ 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. ISSN 0301-4851. PMC 3294216 . PMID 22065248. doi:10.1007/s11033-011-1281-5.
- ↑ 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. ISSN 0021-9258. PMID 18063574. doi:10.1074/jbc.M707411200.
- ↑ 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. ISSN 1932-6203. PMC 4492579 . PMID 26147748. doi:10.1371/journal.pone.0132004.
- ↑ 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): 15458–15461. ISSN 1364-548X. doi:10.1039/C5CC06095H.
- ↑ 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.
- ↑ 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.
- 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. ISSN 1096-987X. doi:10.1002/jcc.20384.
- ↑ 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.
- ↑ 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. ISSN 0264-6021. PMC 1223433 . PMID 12622704. doi:10.1042/bj20021627.
- ↑ 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.
- ↑ 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. PMID 18205296. doi:10.1021/jm070866g.
- ↑ 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. ISSN 0066-4804. PMC 4704194 . PMID 26482303. doi:10.1128/AAC.01335-15.
- ↑ 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.
- ↑ 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.
- ↑ Makena, Anne; Düzgün, Azer Ö; Brem, Jürgen; McDonough, Michael A.; Rydzik, Anna M.; Abboud, Martine I.; Saral, Ayşegül; Çiçek, Ayşegül Ç; Sandalli, Cemal (2016-03-01). "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. ISSN 0066-4804. PMC 4775916 . PMID 26666919. doi:10.1128/AAC.01768-15.
- ↑ Abboud, Martine I.; Damblon, Christian; Brem, Jürgen; Smargiasso, Nicolas; Mercuri, Paola; Gilbert, Bernard; Rydzik, Anna M.; Claridge, Timothy D. W.; Schofield, Christopher J. (2016-07-11). "Interaction of Avibactam with Class B Metallo-β-lactamases". Antimicrobial Agents and Chemotherapy. 60: AAC.00897–16. ISSN 0066-4804. PMC 5038302 . PMID 27401561. doi:10.1128/AAC.00897-16.
- ↑ Makena, Anne; Brem, Jürgen; Pfeffer, Inga; Geffen, Rebecca E. J.; Wilkins, Sarah E.; Tarhonskaya, Hanna; Flashman, Emily; Phee, Lynette M.; Wareham, David W. (2015-02-01). "Biochemical characterization of New Delhi metallo-β-lactamase variants reveals differences in protein stability". Journal of Antimicrobial Chemotherapy. 70 (2): 463–469. ISSN 0305-7453. PMC 4291237 . PMID 25324420. doi:10.1093/jac/dku403.
- ↑ Pettinati, Ilaria; Brem, Jürgen; McDonough, Michael A.; Schofield, Christopher J. (2015-05-01). "Crystal structure of human persulfide dioxygenase: structural basis of ethylmalonic encephalopathy". Human Molecular Genetics. 24 (9): 2458–2469. ISSN 0964-6906. PMC 4383860 . PMID 25596185. doi:10.1093/hmg/ddv007.
- ↑ Council, Biotechnology and Biological Sciences Research. "Research Advisory Panel - BBSRC". www.bbsrc.ac.uk. Retrieved 2017-02-25.
- ↑ "Jeremy Knowles Award 2011 Winner". www.rsc.org. Retrieved 2017-02-25.