Flora Meilleur

Flora Meilleur

Flora Meilleur

Lead Instrument Scientist, IMAGINE diffractometer; Joint Faculty, NCSU Biochemistry

Bio

We primarily use a combination of X-ray and neutron diffraction and scattering to probe enzyme structure, dynamics and function. Our goal is to map intra- and intermolecular interactions that govern enzyme function within the microenvironment of the catalytic site. Knowledge of local electrostatics, hydrogen-bonding networks and protonation states of titratable catalytic residues is essential for proper thermodynamic modeling and for predicting binding interactions in molecular recognition and catalysis.

We are interested in the enzymatic cellulose degradation, a key challenge remaining to be overcome for efficient industrial development of cellulose based products. Understanding how wood degrading organism enzymes function is required to guide enzyme engineering and design of more efficient enzymes. Two types of extracellular enzymatic systems have been identified in microorganisms capable of cellulose degradation: a hydrolytic system and an oxidative system. Our efforts are focused on gaining insight into the structures, dynamics and functions of enzymes from both systems.

We are also interested in understanding cytochrome P450s, one of nature's most versatile biologic catalysts. Cytochromes P450 (P450s) are ubiquitous enzymes catalyzing monooxygenation reactions and playing diverse functional roles in a broad range of biological systems. In mammals they are involved in a variety of biochemical processes including carcinogenesis, drug metabolism, biosynthesis of lipids and steroids or degradation of xenobiotics.

Awards

2013 ORNL Significant Event Award (Team award; Role: Science lead)

Publications

1. O’Dell W.B., Bodenheimer A., Meilleur F. (2016) Neutron Protein Crystallography: A Complementary Tool for Locating Hydrogens in Proteins (Review). Arch. Biochem. Biophys. In press.
2. Knihtila R, Holzapfel G, Weiss K, Meilleur F, Mattos C. (2015) Neutron Crystal Structure of RAS GTPase puts in question the Protonation State of the GTP γ-Phosphate. J. Biol. Chem. http://www.jbc.org/cgi/doi/10.1074/jbc.M115.679860
3. Zhuravleva M., Lindsey A., Chakoumakos B.C., Custelcean R., Meilleur F., Hughes R.W., Kriven W.M., Melcher C.L. (2015) Crystal structure and thermal expansion of a CsCe2Cl7 scintillator. J. Solid State Chem. 227:142-149
4. Golden E., Attwood P.V., Duff A.P., Meilleur F., Vrielink A. (2015) Production and characterization of recombinant perdeuterated cholesterol oxidase. Anal Biochem. 485:102-106
5. Bodenheimer A., Cuneo M., Schwarz P., O’Neill H., Myles D.A., Meilleur F. (2014) Crystallization and preliminary X-ray diffraction analysis of Hypocrea jecorina cel7a in two new crystal forms. Acta Cryst. F70:773-776
6. Munshi P., Snell E.H, Van der Woerd M.J., Judge R.A., Myles D.A., Ren Z., Meilleur F. (2014) Hydrogen bonding interaction at the active site of cyclic glucose bound xylose isomerase E186Q mutant. Acta Cryst. D70:414-420
7. Gruene T., Hahn H.W., Meilleur F., Sheldrick G.M. (2014) Refinement of macomolecular structures against neutron data with SHELXL-2013. J. Appl. Cryst. 47:462-466
8. Meilleur F., Munshi P., Kovalevsky A., Koritsanszky T., Blessing R., Robertson L., Stoica A.D., Crow L., Myles D.A. (2013) IMAGINE: First Neutron Protein Structure and New capabilities for neutron macromolecular crystallography. Acta Cryst. D69:2157-2160
9. Ankner J., Heller W.T., Herwig K., Meilleur F., Myles D.A. (2012) Neutron scattering techniques and application in structural biology. Current Protoc. Prot. Sci. Chapter 17:Unit17:16