Browsing by Author "Meilleur, F"

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    An extended N-H bond, driven by a conserved second-order interaction, orients the flavin N5 orbital in cholesterol oxidase
    (Springer Nature, 2017-01-18) Golden, EA; Yu, LJ; Meilleur, F; Blakeley, MP; Duff, AP; Karton, A; Vrielink, A
    The protein microenvironment surrounding the flavin cofactor in flavoenzymes is key to the efficiency and diversity of reactions catalysed by this class of enzymes. X-ray diffraction structures of oxidoreductase flavoenzymes have revealed recurrent features which facilitate catalysis, such as a hydrogen bond between a main chain nitrogen atom and the flavin redox center (N5). A neutron diffraction study of cholesterol oxidase has revealed an unusual elongated main chain nitrogen to hydrogen bond distance positioning the hydrogen atom towards the flavin N5 reactive center. Investigation of the structural features which could cause such an unusual occurrence revealed a positively charged lysine side chain, conserved in other flavin mediated oxidoreductases, in a second shell away from the FAD cofactor acting to polarize the peptide bond through interaction with the carbonyl oxygen atom. Double-hybrid density functional theory calculations confirm that this electrostatic arrangement affects the N-H bond length in the region of the flavin reactive center. We propose a novel second-order partial-charge interaction network which enables the correct orientation of the hydride receiving orbital of N5. The implications of these observations for flavin mediated redox chemistry are discussed.© The Authors - Creative Commons Attribution 4.0 International License
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    New sources and instrumentation for neutrons in biology
    (Elsevier, 2008-04-18) Teixeira, SCM; Zaccai, G; Ankner, J; Bellissent-Funel, MC; Bewley, RI; Blakeley, MP; Callow, P; Coates, L; Dahint, R; Dalgliesh, R; Dencher, NA; Forsyth, VT; Fragneto, G; Frick, B; Gilles, R; Gutberlet, T; Haertlein, M; Hauß, T; Häußler, W; Heller, WT; Herwig, K; Holderer, O; Juranyi, F; Kampmann, R; Knott, RB; Krueger, S; Langan, P; Lechner, RE; Lynn, GW; Majkrzak, CF; May, RP; Meilleur, F; Mo, Y; Mortensen, K; Myles, DAA; Natali, F; Neylon, C; Niimura, N; Ollivier, J; Ostermann, A; Peters, J; Pieper, J; Rühm, A; Schwahn, D; Shibata, K; Soper, AK; Strässle, T; Suzuki, J; Tanaka, I; Tehei, M; Timmins, P; Torikai, N; Unruh, T; Urban, V; Vavrin, R; Weiss, K
    Neutron radiation offers significant advantages for the study of biological molecular structure and dynamics. A broad and significant effort towards instrumental and methodological development to facilitate biology experiments at neutron sources worldwide is reviewed. © 2008, Elsevier Ltd.
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    Teaching and education highlighted
    (International Union of Crystallography, 2022-04) Dawe, LN; García-Ruiz, JM; Hajdu, J; McIntyre, GJ; Meilleur, F; Stephenson, LL
    The development of the Teaching and Education (T&E) category of articles in Journal of Applied Crystallography, leading to the recent appointment of Louise Dawe as an additional T&E Editor, is described. Louise and ongoing T&E Editor Juan Manuel García-Ruiz outline their vision for the category. Teaching and Education (T&E) was quietly introduced as a new category of article in Journal of Applied Crystallography (JAC) in an editorial by the then Editor Mike Glazer in 1994 (Glazer, 1994).1 The brief for T&E articles in subsequent Notes for Authors was short and fairly broad: ‘Articles in this category cover all aspects of an educational nature related to the general field of crystallography’ © International Union of Crystallography - Open Access
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    Using macromolecular neutron crystallography to study hydrogen atoms in the catalytic mechanism of the FADH cofactor in cholesterol oxidase
    (International Conference on Neutron Scattering, 2017-07-12) Golden, E; Yu, LJ; Meilleur, F; Blakeley, MP; Duff, AP; Karton, A; Vrielink, A
    The protein microenvironment surrounding the flavin cofactor in flavoenzymes is key to the efficiency and diversity of reactions catalysed by this class of enzymes. X-ray diffraction structures of oxidoreductase flavoenzymes have revealed recurrent features which facilitate catalysis, such as a hydrogen bond between a main chain nitrogen atom and the flavin redox center (N5). A neutron diffraction study of cholesterol oxidase has revealed an unusual elongated main chain nitrogen to hydrogen bond distance positioning the hydrogen atom towards the flavin N5 reactive center. Investigation of the structural features which could cause such an unusual occurrence revealed a positively charged lysine side chain, conserved in other flavin mediated oxidoreductases, in a second shell away from the FAD cofactor acting to polarize the peptide bond through interaction with the carbonyl oxygen atom. Double-hybrid density functional theory calculations confirm that this electrostatic arrangement affects the N-H bond length in the region of the flavin reactive center. We propose a novel second-order partial-charge interaction network which enables the correct orientation of the hydride receiving orbital of N5. The implications of these observations for flavin mediated redox chemistry are discussed.