Keywords: Computational Chemical Glycobiology - enzymatic reactivity - carbohydrate-active enzymes - glycosidation - lipoxygenases - computational chemistry
Laura Masgrau received a B.A. degree (1997) and a PhD. (2002) in Chemistry from the Universitat Autònoma de Barcelona. Her thesis, under the supervision of A. Gonzalez-Lafont and J.M. Lluch, focussed on the computational study of atmospheric reactions initiated by the hydroxyl radical. After the thesis, her research moved into the area of enzyme reaction.
She did a 3-years postdoc at the Department of Chemistry and Biochemistry of the University of Leicester, where she worked with M. Sutcliffe, the enzymologist N. Scrutton, the crystallographer D. Leys and in tight collaboration with A. Mulholland from the University of Bristol. Based on a combination of experimental data and QM/MM methods, they investigated the reaction catalysed by two amine dehydrogenases (AADH and MADH). In particular, they studied the rate enhancement of these reactions due to hydrogen tunnelling.
In November 2005 she moved to the Institut Pasteur in Paris as an Intra-European Marie Curie Fellow (2 years). She worked with A. Blondel in the laboratory of M. Nilges at the Department of Structural Biology and Chemistry (Unité de Bioinformatique Structurale).
She came back to Catalonia in early 2008 to work at the Institut de Biotecnologia i de Biomedicina (IBB) at the Universitat Autònoma de Barcelona as a Ramon y Cajal researcher.
Her current research interests reamin in the study of enzymes (reactivity, specificity, affinity, structure, engineering, etc.), with the view of possible biomedical and/or biotechnological applications. Her main research line is the study of carbohydrate-active enzymes, in particular of those involved in the biosynthesis and biodegradation of glycans. Collaborations with the groups of Dr. M. Guerin, Prof. A. Planas and Dr. L. Tabak have been established.
- “QM/MM Studies Reveal How Substrate-Substrate and Enzyme-Substrate Interactions Modulate Retaining Glycosyltransferases Catalysis and Mechanism”, H. Góomez, F. Mendoza, J.M. Lluch and L. Masgrau, Adv. Protein Chem. Struct. Biol., (2015), doi: 10.1016/bs.apcsb.2015.06.004.
- “A Native Ternary Complex Trapped in a crystal Reveals the Catalytic Mechanism of a Retaining Glycosyltransferase”, D. Albesa-Jové, F. Mendoza, A. Rodrigo-Unzueta, F. Gomollon-Bel, J.O. Cifuente, S. Urresti, N. Comino, H. Gómez, J. Romero-Garcia, J.M. Lluch, E. Sancho-Vaello, X. Biarnés, A. Planas, P. Merino, L. Masgrau and M. Guerin, Angew. Chem. Int. Ed., 54, 9898-9902 (2015).
- "The importance of ensemble-averaging in enzyme kinetics", L. Masgrau, D.G. Truhlar, Acc. Chem. Res., 48, 431-438 (2015).
- “Theoretical Study of the Free Energy Surface and Kinteics of the Hepatitis C Virus NS3/NS4A Serine Protease Reactions with the NS5A/5B Substrate. Does the Generally Accepted Tetrahedral Intermediate Really Exist?, J.A. Martínez-González, M. González, L. Masgrau and R. Martínez, ACS Catalysis, 5, 246-255 (2015).
- "Unraveling How Enzymes Can Use Bulky Residues To Drive Site-Selective C-H Ativation: The Case of Mammalian Lipoxygenases Catalyzinf Arachidonic Acid Oxidation", P. Saura, R. Suardíaz, L. Masgrau, J.M. Lluch, À. González-Lafont, ACS Catalysis, 4, 4351-4363 (2014).
- "Regio- and stereospecificity of arachidonic acid oxygenation catalyzed by Leu597 mutants of rabbit 15-lipoxygenase. A QM/MM study", R. Suardíaz, L. Masgrau, J.M. Lluch, À. González-Lafont, FEBS Journal, 281, 636 (2014).
- “Introducing Mutations to Modify the C13/C9 Ratio in Linoleic Acid Oxygenations Catalyzed by Rabbit 15-Lipoxygenase: A QM/MM and MD study”, R. Suardíaz, L. Masgrau, J.M. Lluch, À. González-Lafont, ChemPhysChem , 15, 4049-54 (2014).
- “Computational and experimental study of O-glycosylation. Catalysis by human UDP-GalNAc polypeptide:GalNAc transferase-T2“, H. Gómez, R. Rojas, D. Patel, L. A. Tabak*, J.M. Lluch and L. Masgrau*, Org. Biomol. Chem., 12, 2645-55 (2014) and outside cover.
- “Regio- and Stereospecificity of Arachidonic Acid Oxygenation Catalyzed by Leu597 Mutants of rabbit 15-Lypoxygenases. A Quantum Mechanics/Molecular Mechanics Study”, R. Suardíaz, L. Masgrau, J.M. Lluch, À. González-Lafont, ChemPhysChem 15, 2303-10 (2014).
- “On the Regio- and Stereospecificity of Arachidonic Acid Peroxidation Catalyzed by Mammalian 15-Lypoxygenases: A Combined Molecular Dynamics and QM/MM Study”, R. Suardíaz, L. Masgrau, J.M. Lluch, À. González-Lafont, ChemPhysChem, 14, 3777-3787 (2013).
- “QM/MM study of HCV NS3/NS4A protease with its main substrates: from the structure to the kinetics”, J. Á. Martínez, R. Martínez, M. P. Puyuelo, L. Masgrau, M. González, Eur Biophys J (2013) 42 (Suppl 1):S1–S236 DOI 10.1007/s00249-013-0917-x.
- “On the regiospecificity of hydroperoxidation of fatty acids by mammalian lipoxygenases”, R. Suardíaz, L. Masgrau,J.M. Lluch, À. González-Lafont, FEBS Journal, Supp.1, 280, 94 (2013).
-“Substrate-assisted and nucleophilically assisted catalysis in bovine a1,3-galactosyltransferase. Mechanistic implications for retaining glycosyltransferases”, H. Gómez, J.M. Lluch, L. Masgrau*, J. Am. Chem. Soc., 135, 7053-7063 (2013).
- “An insight into the regiospecificity of linoleic acid peroxidation catalyzed by mammalian 15-lipoxygenase”, R. Suardíaz, L. Masgrau, J.M. Lluch, À. González-Lafont, J. Phys. Chem. B, 117, 3747-3754 (2013).
- “Role of Arg403 for thermostability and catalytic activity of rabbit 12/15-lipoxygenase”, A.Di Venere, T. Horn, S. Stehling, G. Mei, L. Masgrau, À. González-Lafont, H. Kühn, I. Ivanov, Bioch. Biophys. Acta (BBA): Molecular and Cell Biology of Lipids, 1831, 1079-1088 (2013).
- “Essential role of glutamate 317 in galactosyl transfer by a3GalT: a computational study”, H. Gómez, J.M. Lluch, L. Masgrau*, Carbohydr. Research., 356, 204-208 (2012).
- “Retaining glycosyltransferase mechanism studied by QM/MM methods: LgtC transfers alpha-galactose via an oxocarbenium ion-like transition state”, H. Gómez, J.M. Lluch, L. Masgrau*, J. Am. Chem. Soc., 134, 4743-4752 (2012).
-"Influence of the enzyme phosphorilation state and the substrate on PKA enzyme dynamics", M. Montenegro, L. Masgrau, À. González-Lafont, J. M. Lluch and M. Garcia-Viloca, Biophysical Chemistry, 161, 17-28 (2012).
- Substrate binding to mammalian 15-lipoxygenase", L. Toledo, L.Masgrau*, J. M. Lluch and À. González-Lafont*, J. Comput. Aided Mol Des, 25, 825-835 (2011).
- "Ligand induced formation of transient dimmers of mammalian 12/15-lipoxygenase: a key to allosteric behaviour of this class of enzymes?", I. Ivanov, W. Shang, L. Toledo, L. Masgrau, D. I. Svergun, S. Stehling, H. Gómez, A. Di Venere, G. Mei, J. M. Lluch, E. Skrzypczak-Jankun, À. González-Lafont and H. Kühn, Proteins: Structure, Function and Bioinformatics, 69, 521-535 (2011).
- “Insights into the Mechanism of Binding of Arachidonic Acid to Mammalian 15-lipoxygenases”, L. Toledo, L. Masgrau*, J.-D. Maréchal, J.M. Lluch, À. González-Lafont*, J. Phys. Chem. B., 114, 7037-7046 (2010).
- “Natural Mutations of the anti-Müllerian Hormone Type II Receptor found in Persistent Müllerian Duct Syndrome Affect Ligand Binding, Signal Transduction and Cellular Transport”, C. Belville, J.-D. Maréchal, S. Pennetier, P. Carmillo, L. Masgrau, L. Messika-Zeitoun, J.Galey, G. Machado, D. Treton, J. Gonzalès, J.-Y. Picard, N. Josso, R. L. Cate y N. di Clemente, Human Molecular Genetics, 18, p. 3002-3013 (2009).
- “Atomistic insight into the origin of the temperature-dependence of kinetic isotope effects and H-tunnelling in enzyme systems is revealed through combined experimental studies and biomolecular simulation”; S. Hay, C. Pudney, P. Hothi, L.O. Johannissen, L. Masgrau, J. Pang, D. Leys, M. J. Sutcliffe, N. S. Scrutton; Bioch. Soc. Trans. , 36 part 1, 16-21 (2008).
- “New Insights into the Reductive Half-Reaction Mechanism of Aromatic Amine Dehydrogenase Revealed by Reaction with Carbinolamine Substrates “; A. Roujeinikova, P. Hothi, L. Masgrau, M.J. Sutcliffe, N.S. Scrutton, D. Leys; J. Biol. Chem., 282, 23766-23777 ( 2007).
- “Analysis of Classical and Quantum Paths for Deprotonation of Methylamine by Methylamine Dehydrogenase“; K. E. Ranaghan, L. Masgrau, M.J. Sutcliffe, N.S. Scrutton, A.J. Mulholland; ChemPhysChem, 8, 1816-1832 (2007).
- “Tunneling and Classical Paths for Proton Transfer in an Enzyme reaction Dominated by Tunneling: Oxidation of Tryptamine by Aromatic Amine Dehydrogenase”; L. Masgrau, K.E. Ranaghan, N.S. Scrutton, A.J. Mulholland, M.J. Sutcliffe, J. Phys. Chem. B, 111, 3032-3047 (2007).
- “Atomic description of an enzyme reaction dominated by proton tunnelling”; L. Masgrau, A. Roujeinikova, L. O. Johannissen, P. Hothi, J. Basran, K. E. Ranaghan, A. J. Mulholland, M. J. Sutcliffe, N. S. Scrutton, D. Leys; Science, 312, 237-241 (2006).
- “Hydrogen tunnelling in enzyme-catalysed H-transfer reactions: flavoprotein and quinoprotein systems”; M. J. Sutcliffe, L. Masgrau, A. Roujeinikova, L. O. Johannissen, P. Hothi, J. Basran, K. E. Ranaghan, A. J. Mulholland, D. Leys, N. S. Scrutton; Philos. T. Roy. Soc. B, 361, 1375-1386 (2006).
- “Narrowing the gap, a role for protein dynamics in biological quantum tunnelling”; D. Leys, H.S. Toogood, A. Roujeinikova, L. Masgrau, M.J. Sutcliffe, N.S. Scrutton; Eur. Biophys. J., 34, p540 (2005).
- “Hydrogen tunneling in quinoproteins.”; L. Masgrau, J. Basran, P. Hothi, M.J. Sutcliffe, N.S. Scrutton; Archives Biochem. Biophys., 428, 41-51 (2004).
- “The curvature of the Arrhenius plots predicted by conventional canonical transition-state theory in the absence of tunneling”; L. Masgrau, A. González-Lafont, J.M. Lluch; Theor. Chem. Acc., 10, 352 (2003).
- “Dependence of the rate constants on the treatment of internal rotation modes: the reaction OH + CH3SH ® CH3S + H2O as an example”; L. Masgrau, A. González-Lafont, J.M. Lluch; J. Comp. Chem., 24, 701 (2003).
- “Variational transition-state theory rate constant calculations of the OH + CH3SH reaction and several isotopic variants”; L. Masgrau, A. González-Lafont, J.M. Lluch; J. Phys. Chem. A, 107, 4490 (2003).
- “Variational transition-state rate constant calculations with multidimensional tunnelling corrections of the reaction of acetone with OH”; L. Masgrau, A. González-Lafont, J.M. Lluch; J. Phys. Chem. A, 106, 11760 (2002).
- “On the evaluation of quasi-thermodynamic magnitudes from rate constant values. Influence of the variational and tunnelling contributions”; L. Masgrau, A. González-Lafont, J.M. Lluch; Chem. Phys. Lett., 353, 154 (2002).
- “Test of variational transition state theory with multidimensional tunnelling contributions against experimental kinetic isotope effects for the CHnD4-n + OH --> P (n=0,4) reactions”; L. Masgrau, A. González-Lafont, J.M. Lluch; Theor. Chem. Acc., 108, 38 (2002). - “The reactions CHnD4-n + OH --> P and CH4 + OD --> HOD + CH3 as a test of current direct dynamics multicoefficient methods to determine variational transition state rate constants. II”; L. Masgrau, A. González-Lafont, J.M. Lluch; J. Chem. Phys., 115, 4515 (2001).
- “The reactions CHnD4-n + OH --> P and CH4 + OD --> HOD + CH3 as a test of current direct dynamics computational methods to determine variational transition state rate constants. I”; L. Masgrau, A. González-Lafont, J.M. Lluch; J. Chem. Phys., 114, 2154 2001).
-"Effect of a complex formation on the calculated low-pressure rate constant of bimolecular gas-phase reaction governed by tunnelling”; L. Masgrau, A. González-Lafont, J.M. Lluch; J. Comp. Chem., 20, 1685 (1999).
- “Mechanism of the gas-phase HO + H2O à H2O + OH reaction and several associated isotope exchange reactions: a canonical variational transition state theory plus multidimensional tunneling calculation”, L. Masgrau, A. González-Lafont and J.M. Lluch, J. Phys. Chem. A, 103, 1044 (1999).
- “Hydrogen tunnelling in enzyme-catalyzed hydrogen transfer: aspects from flavoprotein catalyzed reactions.”; J. Basran, P. Hothi, L. Masgrau, M.J. Sutcliffe, N.S. Scrutton; in Hydrogen Transfer Reactions, II Biological Aspects, Eds. J. Hynes, J. Klinman, H. Limbach, D. Schowen, Eds.; Wiley_VCH, Weinheim; 2006, ISBN 978-3-527-30777-7
- “Solution and computational studies of kinetic isotope effects in flavoprotein and quinoprotein catalyzed substrate oxidations as probes of enzymic hydrogen tunneling and mechanism”; J. Basran, L. Masgrau, M.J. Sutcliffe, N.S. Scrutton; in Isotope effects in chemistry and biology, A. Kohen & H.H. Limbach Eds.; Taylor & Francis CRC Press, Boca Raton, FL; 2005, ISBN 0824724496.