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Emily Flashman Publications

2018

The plant cysteine oxidases from Arabidopsis thaliana are kinetically tailored to act as oxygen sensors. White MD, Kamps JJAG, East S, Taylor Kearney LJ, Flashman E. J Biol Chem 2018 Jul; 293: 11786-11795. doi:10.1074/jbc.RA118.003496.
YcfDrm is a thermophilic oxygen-dependent ribosomal protein uL16 oxygenase Sekirnik R, Wilkins SE, Bush J, Tarhonskaya H, Munzel M, Hussein A, Flashman E, Mohammed S, McDonough MA, Loenarz C, Schofield CJ. Extremophiles 2018 May; 22: 553-562. doi:10.1007/s00792-018-1016-9.
Lysine-241 has a role in coupling 2OG turnover with substrate oxidation during KDM4-catalysed histone demethylation. Hancock RL, Abboud MI, Smart TJ, Flashman E, Kawamura A, Schofield CJ, Hopkinson RJ. Chembiochem 2018 May; 19: 917-921. doi:10.1002/cbic.201800002.

2017

Molecular and cellular mechanisms of HIF prolyl hydroxylase inhibitors in clinical trials. Yeh TL, Leissing TM, Abboud MI, Thinnes CC, Atasoylu O, Holt-Martyn JP, Zhang D, Tumber A, Lippl K, Lohans CT, Leung IKH, Morcrette H, Clifton IJ, Claridge TDW, Kawamura A, Flashman E, Lu X, Ratcliffe PJ, Chowdhury R, Pugh CW, Schofield CJ. Chem Sci. 2017 Sept; 8: 7651-7668. doi.org/10.1039/C7SC02103H.
Studies on the interaction of the histone demethylase KDM5B with tricarboxylic acid cycle intermediates. Tarhonskaya H, Nowak RP, Johansson C, Szykowska A, Tumber A, Hancock RL, Lang P, Flashman E, Oppermann U, Schofield CJ, Kawamura A. J Mol Biol. 2017 Sept; 429: 2895-2906. doi.org/10.1016/j.jbm.2017.08.007.
Ribonucleotide reductase requires subunit switching in hypoxia to maintain DNA replication. Foskolou IP, Jorgensen C, Leszczynska KB, Olcina MM, Tarhonskaya H, Haisma B, D'Angiolella V, Myers WK, Domene C, Flashman E, Hammond EM. Mol Cell. 2017 Apr; 66: 206-220. doi.org/10.1016/j.molcel.2017.03.005.
Plant cysteine oxidases are dioxygenases that directly enable arginyl transferase-catalysed arginylation of N-end rule targets. White MD, Klecker M, Hopkinson RJ, Weits DA, Mueller C, Naumann C, O'Neill R, Wickens J, Yang J, Brooks-Bartlett JC, Garman EF, Grossmann TN, Dissmeyer N, Flashman E. Nat Commun. 2017 Mar; 8: 14690. doi:10.1038/ncomms14690.
The activity of JmjC histone lysine demethylase KDM4A is highly sensitive to oxygen concentrations. Hancock RL, Masson N, Dunne K, Flashman E, Kawamura A. ACS Chem Biol. 2017 Apr; 12: 1011-1019. doi:10.1021/acschembio.6b00958.

2016

Use of ferrous iron by metallo-β-lactamases. Cahill ST, Tarhonskaya H, Rydzik AM, Flashman E, McDonough MA, Schofield CJ, Brem J. J Inorg Biochem. 2016 Oct; 163: 185-193. doi:10.1016/j.jinorgbio.2016.07.013.
Catalytic Strategies of the Non-Heme Iron-Dependent Oxygenases and their Roles in Plant Biology. White MD, Flashman E. Curr Opin Chem Biol. Available online 23 March 2016. doi:10.1016/j.cbpa.2016.02.017.

2015

Structure and Mechanism of a Viral Collagen Prolyl Hydroxylase. Longbotham JE, Levy C, Johannissen LO, Tarhonskaya H, Jiang S, Loenarz C, Flashman E, Hay S, Schofield CJ, Scrutton NJ. Biochemistry. 2015 Oct 6; 54(39):6093-105. doi: 10.1021/acs.biochem.5b00789.
Kinetic Investigations of the Role of Factor Inhibiting Hypoxia-Inducible Factor (FIH) as an Oxygen Sensor. Tarhonskaya H, Hardy AP, Howe EA, Loik ND, Kramer HB, McCullagh JS, Schofield CJ, Flashman E. J Biol Chem. 2015 Aug 7; 290(32):19726-42. doi:pii: jbc.M115.653014.
Epigenetic regulation by histone demethylases in hypoxia. Hancock RL, Dunne K, Walport LJ, Flashman E, Kawamura A. Epigenomics 2015 Aug; 7(5):791-811. doi: 10.2217/epi.15.24.
Studying the active-site loop movement of the São Paolo metallo-β-lactamase-1. Brem J, Struwe WB, Rydzik AM, Tarhonskaya H, Pfeffer I, Flashman E, van Berkel SS, Spencer J, Claridge TD, McDonough MA, Benesch JL, Schofield CJ. Chem Sci. 2015 Feb 19;6(2):956-963.

2014

Biochemical characterization of New Delhi metallo-β-lactamase variants reveals differences in protein stability. Makena A, Brem J, Pfeffer I, Geffen RE, Wilkins SE, Tarhonskaya H, Flashman E, Phee LM, Wareham DW, Schofield CJ. J Antimicrob Chemother. 2014 Oct 16. doi:pii: dku403. [Epub ahead of print]
Investigating the contribution of the active site environment to the slow reaction of hypoxia-inducible factor prolyl hydroxylase domain 2 with oxygen. Tarhonskaya H, Chowdhury R, Leung IK, Loik ND, McCullagh JS, Claridge TD, Schofield CJ, Flashman E. Biochem J. 2014 Nov 1;463(3):363-72. doi: 10.1042/BJ20140779.
Studies on deacetoxycephalosporin C synthase support a consensus mechanism for 2-oxoglutarate dependent oxygenases.Tarhonskaya H, Szöllössi A, Leung IK, Bush JT, Henry L, Chowdhury R, Iqbal A, Claridge TD, Schofield CJ, Flashman E.Biochemistry. 2014 Apr 22;53(15):2483-93. doi: 10.1021/bi500086p. Epub 2014 Apr 11.
Non-enzymatic chemistry enables 2-hydroxyglutarate-mediated activation of 2-oxoglutarate oxygenases.Tarhonskaya H, Rydzik AM, Leung IK, Loik ND, Chan MC, Kawamura A, McCullagh JS, Claridge TD, Flashman E, Schofield CJ.Nat Commun. 2014 Mar 5;5:3423. doi: 10.1038/ncomms4423.
OGFOD1 catalyzes prolyl hydroxylation of RPS23 and is involved in translation control and stress granule formation.Singleton RS, Liu-Yi P, Formenti F, Ge W, Sekirnik R, Fischer R, Adam J, Pollard PJ, Wolf A, Thalhammer A, Loenarz C, Flashman E, Yamamoto A, Coleman ML, Kessler BM, Wappner P, Schofield CJ, Ratcliffe PJ, Cockman ME.Proc Natl Acad Sci U S A. 2014 Mar 18;111(11):4031-6. doi: 10.1073/pnas.1314482111. Epub 2014 Feb 18.

2013

Investigations on the oxygen dependence of a 2-oxoglutarate histone demethylase.Sánchez-Fernández EM, Tarhonskaya H, Al-Qahtani K, Hopkinson RJ, McCullagh JS, Schofield CJ, Flashman E.Biochem J. 2013 Jan 15;449(2):491-6. doi: 10.1042/BJ20121155.

2011

Studies on the reaction of nitric oxide with the hypoxia-inducible factor prolyl hydroxylase domain 2 (EGLN1).Chowdhury R, Flashman E, Mecinović J, Kramer HB, Kessler BM, Frapart YM, Boucher JL, Clifton IJ, McDonough MA, Schofield CJ.J Mol Biol. 2011 Jul 8;410(2):268-79. doi: 10.1016/j.jmb.2011.04.075. Epub 2011 May 13.

2010

Evidence for the slow reaction of hypoxia-inducible factor prolyl hydroxylase 2 with oxygen.Flashman E, Hoffart LM, Hamed RB, Bollinger JM Jr, Krebs C, Schofield CJ.FEBS J. 2010 Oct;277(19):4089-99. doi: 10.1111/j.1742-4658.2010.07804.x. Epub 2010 Aug 31.
Using NMR solvent water relaxation to investigate metalloenzyme-ligand binding interactions.Leung IK, Flashman E, Yeoh KK, Schofield CJ, Claridge TD.J Med Chem.2010 Jan 28;53(2):867-75. doi: 10.1021/jm901537q.

2009

Structural basis for binding of hypoxia-inducible factor to the oxygen-sensing prolyl hydroxylases.Chowdhury R, McDonough MA, Mecinović J, Loenarz C, Flashman E, Hewitson KS, Domene C, Schofield CJ.Structure. 2009 Jul 15;17(7):981-9. doi: 10.1016/j.str.2009.06.002.
Use of mass spectrometry to probe the nucleophilicity of cysteinyl residues of prolyl hydroxylase domain 2.Mecinović J, Chowdhury R, Flashman E, Schofield CJ.Anal Biochem. 2009 Oct 15;393(2):215-21. doi: 10.1016/j.ab.2009.06.029. Epub 2009 Jun 27.
Direct analysis of enzyme-catalyzed DNA demethylation.Karkhanina AA, Mecinović J, Musheev MU, Krylova SM, Petrov AP, Hewitson KS, Flashman E, Schofield CJ, Krylov SN.Anal Chem. 2009 Jul 15;81(14):5871-5. doi: 10.1021/ac9010556.
Application of a proteolysis/mass spectrometry method for investigating the effects of inhibitors on hydroxylase structure.Stubbs CJ, Loenarz C, Mecinović J, Yeoh KK, Hindley N, Liénard BM, Sobott F, Schofield CJ, Flashman E.J Med Chem. 2009 May 14;52(9):2799-805. doi: 10.1021/jm900285r.
Evidence for a stereoelectronic effect in human oxygen sensing.Loenarz C, Mecinović J, Chowdhury R, McNeill LA, Flashman E, Schofield CJ.Angew Chem Int Ed Engl. 2009;48(10):1784-7. doi: 10.1002/anie.200805427.

2008

Dynamic states of the DNA repair enzyme AlkB regulate product release.Bleijlevens B, Shivarattan T, Flashman E, Yang Y, Simpson PJ, Koivisto P, Sedgwick B, Schofield CJ, Matthews SJ.EMBO Rep. 2008 Sep;9(9):872-7. doi: 10.1038/embor.2008.120. Epub 2008 Jul 11.
Crystal structure of the C1 domain of cardiac myosin binding protein-C: implications for hypertrophic cardiomyopathy.Govada L, Carpenter L, da Fonseca PC, Helliwell JR, Rizkallah P, Flashman E, Chayen NE, Redwood C, Squire JM.J Mol Biol. 2008 Apr 25;378(2):387-97. doi: 10.1016/j.jmb.2008.02.044. Epub 2008 Mar 4.
Support for a trimeric collar of myosin binding protein C in cardiac and fast skeletal muscle, but not in slow skeletal muscle.Flashman E, Korkie L, Watkins H, Redwood C, Moolman-Smook JC.FEBS Lett. 2008 Feb 6;582(3):434-8. doi: 10.1016/j.febslet.2008.01.004. Epub 2008 Jan 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.Flashman E, Bagg EA, Chowdhury R, Mecinović J, Loenarz C, McDonough MA, Hewitson KS, Schofield CJ.J Biol Chem. 2008 Feb 15;283(7):3808-15. Epub 2007 Dec 5.
ESI-MS studies on prolyl hydroxylase domain 2 reveal a new metal binding site.Mecinović J, Chowdhury R, Liénard BM, Flashman E, Buck MR, Oldham NJ, Schofield CJ.ChemMedChem. 2008 Apr;3(4):569-72.

2007

The most versatile of all reactive intermediates?Flashman E, Schofield CJ.Nat Chem Biol. 2007 Feb;3(2):86-7.
Studies on the activity of the hypoxia-inducible-factor hydroxylases using an oxygen consumption assay.Ehrismann D, Flashman E, Genn DN, Mathioudakis N, Hewitson KS, Ratcliffe PJ, Schofield CJ.Biochem J. 2007 Jan 1;401(1):227-34.

2006

Cellular oxygen sensing: Crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2).McDonough MA, Li V, Flashman E, Chowdhury R, Mohr C, Lénard BM, Zondlo J, Oldham NJ, Clifton IJ, Lewis J, McNeill LA, Kurzeja RJ, Hewitson KS, Yang E, Jordan S, Syed RS, Schofield CJ.Proc Natl Acad Sci U S A. 2006 Jun 27;103(26):9814-9. Epub 2006 Jun 16.

2005

Hypoxia-inducible factor prolyl hydroxylase 2 has a high affinity for ferrous iron and 2-oxoglutarate.McNeill LA, Flashman E, Buck MR, Hewitson KS, Clifton IJ, Jeschke G, Claridge TD, Ehrismann D, Oldham NJ, Schofield CJ.Mol Biosyst. 2005 Oct;1(4):321-4. Epub 2005 Aug 22.
OS-9: another piece in the HIF complex story.Flashman E, McDonough MA, Schofield CJ.Mol Cell. 2005 Feb 18;17(4):472-3. Review.

2004

Cardiac myosin binding protein C: its role in physiology and disease.Flashman E, Redwood C, Moolman-Smook J, Watkins H.Circ Res. 2004 May 28;94(10):1279-89. Review.

2002

Identification of novel interactions between domains of Myosin binding protein-C that are modulated by hypertrophic cardiomyopathy missense mutations.Moolman-Smook J, Flashman E, de Lange W, Li Z, Corfield V, Redwood C, Watkins H.Circ Res. 2002 Oct 18;91(8):704-11.

2001

Critical role for IL-4 in the development of transplant arteriosclerosis in the absence of CD40-CD154 costimulation.Ensminger SM, Spriewald BM, Sorensen HV, Witzke O, Flashman EG, Bushell A, Morris PJ, Rose ML, Rahemtulla A, Wood KJ.J Immunol. 2001 Jul 1;167(1):532-41.

2000