Flashman Group




Oxygen-sensing mechanisms across eukaryotic kingdoms and their roles in complex multicellularity. Hammarlund EU, Flashman E, Mohlin S, Licausi F (2020) Science. 370:eaba3512.

Structures of Arabidopsis thaliana oxygen-sensing plant cysteine oxidases 4 and 5 enable targeted manipulation of their activity. White M, Dalle Carbonare L, Lavilla Puerta M, Iacopino S, Edwards M, Dunne K, Pires E, Levy C, McDonough M, Licausi F, Flashman E (2020) PNAS117:2314



Masson N, Keeley TP, Giuntoli B, White MD, Puerta ML, Perata P, Flashman E, Licausi F, Ratcliffe PJ (2019). Conserved N-terminal cysteine dioxygenases transduce responses to hypoxia in animals and plants. Science. 365:65.

Dalle Carbonare L, White M, Francini A, Shukla V, Perata P, Flashman E, Sebastiani L, Licausi  F (2019). Zinc excess induces a hypoxia-like response by inhibiting cysteine oxidases in poplar roots. Plant Physiol. 180:1614.

Bush JT, Leśniak RK, Yeh TL, Belle R, Kramer H, Tumber A, Chowdhury R, Flashman E, Mecinović J, Schofield CJ (2019). Small-molecules that covalently react with a human prolyl hydroxylase - towards activity modulation and substrate capture. Chem Commun. 55:1020-1023



Gibbs DJ, Tedds HM, Labandera AM, Bailey M, White MD, Hartman S, Sprigg C, Mogg SL, Osborne R, Dambire C, Boeckx T, Paling Z, Voesenek LACJ, Flashman E, Holdsworth MJ (2018). Oxygen-dependent proteolysis regulates the stability of angiosperm polycomb repressive complex 2 subunit VERNALIZATION 2. Nat Commun 9:5438.

White MD, Kamps JJAG, East S, Taylor Kearney LJ, Flashman E (2018). The plant cysteine oxidases from Arabidopsis thaliana are kinetically tailored to act as oxygen sensors. J Biol Chem 293:11786.

Hancock RL, Abboud MI, Smart TJ, Flashman E, Kawamura A, Schofield CJ, Hopkinson RJ (2018). Lysine-241 has a role in coupling 2OG turnover with substrate oxidation during KDM4-catalysed histone demethylation. Chembiochem. 19:917-921.

Sekirnik R, Wilkins SE, Bush J, Tarhonskaya H, Münzel M, Hussein A, Flashman E, Mohammed S, McDonough MA, Loenarz C, Schofield CJ (2018). YcfDRM is a thermophilic oxygen-dependent ribosomal protein uL16 oxygenase. Extremophiles. 22: 553-562.



Foskolou IP, Jorgensen C, Leszczynska KB, Olcina MM, Tarhonskaya H, Haisma B, D’Angiolella V, Myers WK, Domene C, Flashman E, Hammond EM (2017). Ribonucleotide reductase requires subunit switching in hypoxia to maintain DNA replication. Mol Cell. 66: 206-220                                                                                   

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 (2017). Plant cysteine oxidases are dioxygenases that directly enable arginyl transferase-catalysed arginylation of N-end rule targets. Nat Commun. 8:14690.                                                                                                   

Hancock RL, Masson N, Dunne K, Flashman E, Kawamura A (2017). The activity of JmjC histone lysine demethylase KDM4A is highly sensitive to oxygen concentrations. ACS Chem Biol. doi: 10.1021/acschembio.6b00958.     

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 (2017). Molecular and cellular mechanisms of HIF prolyl hydroxylase inhibitors in clinical trials. Chem Sci. 8: 7651.         

Tarhonskaya H, Nowak RP, Johansson C, Szykowska A, Tumber A, Hancock RL, Lang P, Flashman E, Oppermann U, Schofield CJ, Kawamura A (2017). Studies on the interaction of the histone demethylase KDM5B with tricarboxylic acid intermediates. J Mol Biol. 429: 2895.                                                                        



Cahill ST, Tarhonskaya H, Rydzik AM, Flashman E, McDonough MA, Schofield CJ, Brem J (2016). Use of ferrous iron by metallo-β-lactamases. J Inorg Biochem. 163: 185-193.                                                       

White MD and Flashman E (2016). Catalytic strategies of the non-heme iron dependent oxygenases and their roles in plant biology. Curr Opin Chem Biol.31: 126-135.  



Longbotham JE, Levy C, Johannissen LO, Tarhonskaya H, Jiang S, Loenarz C, Flashman E, Hay S, Schofield CJ, Scrutton NS (2015). Structure and mechanism of a viral collagen prolyl hydroxylase. Biochemistry. 54: 6093-6105.                                                                         

Tarhonskaya H, Hardy AP, Howe EA, Loik ND, Kramer HB, McCullagh JS, Schofield CJ, Flashman E (2015). Kinetic investigations of the role of factor inhibiting hypoxia-inducible factor (FIH) as an oxygen sensor. J Biol Chem. 290: 19726-19742.                                         

Hancock RL, Dunne K, Walport LJ, Flashman E, Kawamura A (2015). Epigenetic regulation by histone demethylases in hypoxia. Epigenomics. 7: 791-811.                                                                             

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 (2015). Studying the active-site loop movement of the São Paolo metallo-β-lactamase. Chem Sci. 6: 956-963.  

Makena A, Brem J, Pfeffer I, Geffen RE, Wilkins SE, Tarhonskaya H, Flashman E, Phee LM, Wareham DW, Schofield CJ (2015). Biochemical characterization of New Delhi metallo-β-lactamase variants reveals differences in protein stability. J Antimicrob Chemother. 70: 463-469.                         



Tarhonskaya H, Chowdhury R, Leung IK, Loik ND, McCullagh JS, Claridge TD, Schofield CJ and Flashman E (2014). Investigating the contribution of the active site environment to the slow reaction of hypoxia-inducible factor prolyl hydroxylase domain 2 with oxygen. Biochem J. 463: 363-372.                                    

Tarhonskaya H, Szöllössi A, Leung IK, Bush JT, Henry L, Chowdhury R, Iqbal A, Claridge TD, Schofield CJ and Flashman E (2014). Studies on deacetoxycephalosporin C synthase support a consensus mechanism for 2-oxoglutarate dependent oxygenases. Biochemistry. 53: 2483-2493.                                                   

Tarhonskaya H, Rydzik AM, Leung IK, Loik ND, Chan MC, Kawamura A, McCullagh JS, Claridge TD, Flashman E and Schofield CJ (2014). Non-enzymatic chemistry enables 2-hydroxyglutarate-mediated activation of 2-oxoglutarate oxygenases. Nat Commun. 5: 3423.                                                                                 

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 (2014). OGFOD1 catalyzes prolyl hydroxylation of RPS23 and is involved in translation control and stress granule formation. Proc Natl Acad Sci U S A. 111:4031-4036.  



Sanchez-Fernandez EM, Tarhonskaya H, Al-Qahtani K, Hopkinson RJ, McCullagh JS, Schofield CJ, Flashman E (2013). Investigations on the oxygen dependence of a 2-oxoglutarate histone demethylase. Biochem J. 449: 491-496.                                                                                                                              


Chowdhury R, Flashman E, Mecinović J, Kramer HB, Kessler BM, Frapart YM, Boucher JL, Clifton IJ, McDonough MA, Schofield CJ (2011). Studies on the reaction of nitric oxide with the hypoxia-inducible factor prolyl hydroxylase domain 2 (EGLN1). J Mol Biol. 410: 268-279.         



Flashman E, Hoffart LM, Hamed RB, Bollinger Jr JM, Krebs C, Schofield CJ (2010). Evidence for the slow reaction of hypoxia-inducible factor prolyl hydroxylase 2 with oxygen. FEBS J. 277: 4089-4099                         

Flashman E, Davies SL, Yeoh KK, Schofield CJ (2010). Investigating the dependence of the hypoxia-inducible factor hydroxylases (factor inhibiting HIF and prolyl hydroxylase domain 2) on ascorbate and other reducing agents. Biochem J. 427: 135-142.                      

Leung IK, Flashman E, Yeoh KK, Schofield CJ, Claridge TD (2010). Using NMR solvent water relaxation to investigate metalloenzyme-ligand binding interactions. J Med Chem. 53: 867-875.                         



Chowdhury R, McDonough MA, Mecinović J, Loenarz C, Flashman E, Hewitson KS, Domene C, Schofield CJ (2009). Structural basis for binding of hypoxia-inducible factor to the oxygen-sensing prolyl hydroxylases. Structure. 17: 981-989.                                                   

Mecinović J, Chowdhury R, Flashman E, Schofield CJ (2009). Use of mass spectrometry to probe the nucleophilicity of cysteinyl residues of prolyl hydroxylase domain 2. Anal Biochem. 393: 215-221.          

Karkhanina AA, Mecinović J, Musheev MU, Krylova SM, Petrov AP, Hewitson KS, Flashman E, Schofield CJ, Krylov SN (2009). Direct analysis of enzyme-catalyzed DNA demethylation. Anal Chem. 81: 5871-5875.

Stubbs CJ, Loenarz C, Mecinović J, Yeoh KK, Hindley N, Liénard BM, Sobott F, Schofield CJ, Flashman E (2009). Application of a proteolysis/mass spectrometry method for investigating the effects of inhibitors on hydroxylase structure. J Med Chem. 52: 2799-2805.                                                                                      

Loenarz C, Mecinović J, Chowdhury R, McNeill LA, Flashman E, Schofield CJ (2009). Evidence for a stereoelectronic effect in human oxygen sensing. Angew Chem Int Ed Engl. 48:1784-178.                 



Bleijlevens B, Shivarattan T, Flashman E, Chen HA, Simpson PJ, Sedgwick B, Schofield CJ and Matthews SJ (2008). Dynamic states of the DNA repair enzyme AlkB regulate product release. EMBO Rep 9: 872-7.    

Loenarz C, Chowdhury R, Schofield CJ and Flashman E (2008). Oxygenases for oxygen sensing. Pure Appl. Chem. 8: 1837-1847.           

Flashman E, Bagg EAL, Chowdhury R, Mecinović J, Loenarz C, McDonough MA, Hewitson KS and Schofield CJ (2008). Kinetic rationale for selectivity towards N- and C-terminal oxygen dependent degradation domain substrates mediated by a loop region of the HIF prolyl hydroxylases. J Biol Chem. 283: 3808-3815.     

Govada L, Carpenter E, da Fonseca PCA, Helliwell J, Rizkallah P, Flashman E, Chayen NE, Redwood C and Squire JM (2008). Crystal Structure of the C1 domain of Cardiac Myosin Binding Protein-C: Implications for Hypertrophic Cardiomyopathy. J Mol Biol. 378: 387-397.                                                                             

Flashman E, Korkie L, Watkins H, Redwood C and Moolman-Smook JC (2008). Support for a trimeric collar of myosin binding protein C in cardiac and fast skeletal muscle, but not slow skeletal muscle. FEBS Lett. 582: 434-438.                                                              

Mecinović J, Chowdhury R, Liénard BM, Flashman E, Buck MR, Oldham NJ, Schofield CJ (2008). ESI-MS Studies on Prolyl Hydroxylase Domain 2 Reveal a New Metal Binding Site. Chem Med Chem3: 569-572.   



Flashman E and Schofield CJ (2007).  The most versatile of all reactive intermediates? Nat Chem Biol 3: 86-87.  Commentary.                                                                                                                                                

Ehrismann D, Flashman E, Genn DN, Mathioudakis N, Hewitson KS, Ratcliffe PJ and Schofield CJ (2007).  Studies on the activity of the hypoxia-inducible factor hydroxylases using an oxygen consumption assay. Biochem J. 401: 227-234.                                                                                                                                                 

Flashman E, Watkins H and Redwood C (2007). Localisation of the binding site of the C-terminal domain of cardiac Myosin Binding Protein-C on the myosin rod.  Biochem J. 401: 97-102.         



McDonough MA, Li V, Flashman E, Chowdhury R, Mohr C, Leinard BM, Zondlo J, Oldham NJ, Clifton IJ, Lewis J, McNeill LA, Kurjeza R, Hewitson KS, Yang E, Jordan S, Syed R and Schofield CJ (2006).  Cellular oxygen sensing: Crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2). Proc. Natl. Acad. Sci. U.S.A. 103: 9814-9819.                                                                                                                                      


McNeill LA, Flashman E­, Buck MRG, Hewitson KS, Clifton IJ, Jeschke G, Claridge TDW, Ehrismann D, Oldham NJ and Schofield CJ (2005). Hypoxia-inducible factor prolyl hydroxylase 2 has a high affinity for ferrous iron and 2-oxoglutarate. Mol Biosys. 1: 321-324.      

Flashman E, McDonough MA and Schofield CJ (2005). OS-9: another piece in the HIF complex story. Mol Cell. 17: 472-473.                                                                                                                                           


Flashman E, Redwood C, Moolman-Smook J and Watkins H (2004). Cardiac myosin binding protein-C: its role in physiology and disease.  Circ Res. 94: 1279-1289.             



Moolman-Smook JC, Flashman E, de Lange W, Corfield V, Redwood C and Watkins H (2002). Identification of novel interactions between domains of myosin binding protein-C that are modulated by hypertrophic cardiomyopathy missense mutations. Circ Res. 91: 704-711.                 



Ensminger SM, Spriewald BM, Sorensen HV, Witzke O, Flashman EG, Bushell A, Morris PJ, Rose ML, Rahemtulla A and Wood KJ (2001). Critical role for IL-4 in the development of transplant arteriosclerosis in the absence of CD40-CD154 costimulation. J Immunol. 167: 532-541.       



Fox KR, Flashman E and Gowers DM (2000). Secondary binding sites for triplex-forming oligonucleotides containing bulges, loops, and mismatches in the third strand. Biochemistry. 39: 6714-6725.