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Your search keyword '"Blumberger, J"' showing total 4 results
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4 results on '"Blumberger, J"'

1. Mechanism of O2 diffusion and reduction in FeFe hydrogenases

Author

Philippe Soucaille, Matteo Sensi, Christophe Léger, Isabelle Meynial-Salles, Charles Gauquelin, Carole Baffert, Jochen Blumberger, Laure Saujet, Robert B. Best, David De Sancho, Adam Kubas, Christophe Orain, Hervé Bottin, Vincent Fourmond, Kubas, A, Orain, C, Sancho, D, Saujet, L, Sensi, M, Gauquelin, C, Meynial-Salles, I, Soucaille, P, Bottin, H, Baffert, C, Fourmond, V, Best, R, Blumberger, J, Léger, C, Department of Physics and Astronomy [UCL London], University College of London [London] ( UCL ), Bioénergétique et Ingénierie des Protéines ( BIP ), Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Chemistry [Cambridge, UK], University of Cambridge [UK] ( CAM ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), Institut de Biologie et de Technologies de Saclay ( IBITECS ), Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés ( LISBP ), Institut National de la Recherche Agronomique ( INRA ) -Institut National des Sciences Appliquées - Toulouse ( INSA Toulouse ), Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Centre National de la Recherche Scientifique ( CNRS ), and Institut de Microbiologie de la Méditerranée ( IMM )

Subjects
Hydrogenase, General Chemical Engineering, Mutant, Nanotechnology, Molecular Dynamics Simulation, Molecular Dynamics, 010402 general chemistry, Electrochemistry, [ CHIM ] Chemical Sciences, 01 natural sciences, Catalysis, Diffusion, Molecular dynamics, Metalloproteins, Site-Directed, Clostridium, CHIM/03 - CHIMICA GENERALE E INORGANICA, chemistry.chemical_classification, biology, 010405 organic chemistry, Chemistry, Mutagenesis, Active site, Electrochemical Techniques, General Chemistry, 0104 chemical sciences, Oxygen, CHIM/02 - CHIMICA FISICA, Enzyme mecanisms, Enzyme, Hydrogen, Mutagenesis, Site-Directed, Oxidation-Reduction, Quantum Theory, Density functional theory, Electrocatalysis, Enzyme mechanisms, Metalloproteins, Molecular dynamics, Density functional theory, Biophysics, biology.protein, Electrocatalysis, Cysteine
Abstract

International audience; FeFe hydrogenases are the most efficient H2-producing enzymes. However, inactivation by O2 remains an obstacle that prevents them being used in many biotechnological devices. Here, we combine electrochemistry, site-directed mutagenesis, molecular dynamics and quantum chemical calculations to uncover the molecular mechanism of O2 diffusion within the enzyme and its reactions at the active site. We propose that the partial reversibility of the reaction with O2 results from the four-electron reduction of O2 to water. The third electron/proton transfer step is the bottleneck for water production, competing with formation of a highly reactive OH radical and hydroxylated cysteine. The rapid delivery of electrons and protons to the active site is therefore crucial to prevent the accumulation of these aggressive species during prolonged O2 exposure. These findings should provide important clues for the design of hydrogenase mutants with increased resistance to oxidative damage.

Published
2016
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2. Combining experimental and theoretical methods to learn about the reactivity of gas-processing metalloenzymes

Author

Claudio Greco, Vincent Fourmond, Po-hung Wang, Sébastien Dementin, Carole Baffert, Maurizio Bruschi, Patrick Bertrand, Luca De Gioia, Christophe Léger, Jochen Blumberger, Department of Earth and Environmental Sciences, Università degli Studi di Milano-Bicocca [Milano], Institut de Microbiologie de la Méditerranée ( IMM ), Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Institute of Oceanography [Taipei], National Taiwan University [Taiwan] ( NTU ), Dipartimento di Biotecnologie e Bioscienze, Department of Physics and Astronomy [UCL London], University College of London [London] ( UCL ), Department of Earth and Environmental Sciences [Milano], Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Institut de Microbiologie de la Méditerranée (IMM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), National Taiwan University [Taiwan] (NTU), University College of London [London] (UCL), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Greco, C, Fourmond, V, Baffert, C, Wang, P, Dementin, S, Bertrand, P, Bruschi, M, Blumberger, J, DE GIOIA, L, and Léger, C

Subjects
enzymes, Context (language use), [CHIM.INOR]Chemical Sciences/Inorganic chemistry, DFT, theoretical chemistry, bioinorganic chemistry, Molecular level, catalytic power of enzymes, computational chemistry, spectroscopy, Computational chemistry, Theoretical chemistry, Environmental Chemistry, Reactivity (chemistry), [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Renewable Energy, Sustainability and the Environment, Chemistry, [ CHIM.INOR ] Chemical Sciences/Inorganic chemistry, Pollution, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, QMMM, Nuclear Energy and Engineering, electrochemistry, Protein film voltammetry, Theoretical methods, [ CHIM.THEO ] Chemical Sciences/Theoretical and/or physical chemistry, Physical chemistry, Experimental methods
Abstract

International audience; After enzymes were first discovered in the late XIX century, and for the first seventy years of enzymology, kinetic experiments were the only source of information about enzyme mechanisms. Over the following fifty years, these studies were taken over by approaches that give information at the molecular level, such as crystallography, spectroscopy and theoretical chemistry (as emphasized by the Nobel Prize in Chemistry awarded last year to M. Karplus, M. Levitt and A. Warshel). In this review, we thoroughly discuss the interplay between the information obtained from theoretical and experimental methods, by focussing on enzymes that process small molecules such as H 2 or CO 2 (hydrogenases, CO-dehydrogenase and carbonic anhydrase), and that are therefore relevant in the context of energy and environment. We argue that combining theoretical chemistry (DFT, MD, QM/MM) and detailed investigations that make use of modern kinetic methods, such as protein film voltammetry, is an innovative way of learning about individual steps and/or complex reactions that are part of the catalytic cycles. We illustrate this with recent results from our labs and others, including studies of gas transport along substrate channels, long range proton transfer, and mechanisms of catalysis, inhibition or inactivation. Broader context Some reactions which are very important in the context of energy and environment, such as the conversion between CO and CO2 , or H+ and H2 , are catalyzed in living organisms by large and complex enzymes that use inorganic active sites to transform substrates, chains of redox centers to transfer electrons, ionizable amino acids to transfer protons, and networks of hydrophobic cavities to guide the diffusion of substrates and products within the protein. This highly sophisticated biological plumbing and wiring makes turnover frequencies of thousands of substrate molecules per second possible. Understanding the molecular details of catalysis is still a challenge. We explain in this review how a great deal of information can be obtained using an interdisciplinary approach that combines state-of-the art kinetics and computational chemistry. This differs from—and complements—the more traditional strategies that consist in trying to see the catalytic intermediates using methods that rely on the interaction between light and matter, such as X-ray diffraction and spectroscopic techniques.

Published
2014
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3. The oxidative inactivation of FeFe hydrogenase reveals the flexibility of the H-cluster

Author

Isabelle Meynial-Salles, Jochen Blumberger, Vincent Fourmond, Carole Baffert, Marco Montefiori, Luca De Gioia, Pierre Ezanno, Claudio Greco, Philippe Soucaille, Kateryna Sybirna, Po-hung Wang, Hervé Bottin, Christophe Léger, Maurizio Bruschi, Bioénergétique et Ingénierie des Protéines (BIP ), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Department of Earth and Environmental Sciences [Milano], Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Service de Bioénergétique, Biologie Stucturale, et Mécanismes (SB2SM), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie et de Technologies de Saclay (IBITECS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Department of Physics and Astronomy [UCL London], University College of London [London] (UCL), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Department of Biotechnologies and Biosciences, Centre National de la Recherche Scientifique, Aix-Marseille Universite, Agence Nationale de la Recherche [ANR-12-BS08-0014, ANR-2010-BIOE-004], Ministero dell'Istruzione, dell'Universita e della Ricerca [Prin 2010M2JARJ], Ministry of Education, Republic of China (Taiwan), Engineering and Physical Sciences Research Council [EP/J015571/1, EP/F067496], Royal Society, Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay, Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), University of Milano-Bicocca, Fourmond, V, Greco, C, Sybirna, K, Baffert, C, Wang, P, Ezanno, P, Montefiori, M, Bruschi, M, Meynial Salles, I, Soucaille, P, Blumberger, J, Bottin, H, DE GIOIA, L, Léger, C, Bioénergétique et Ingénierie des Protéines ( BIP ), Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Earth and Environmental Sciences ( DEES ), Service de Bioénergétique, Biologie Stucturale, et Mécanismes ( SB2SM ), Centre National de la Recherche Scientifique ( CNRS ) -Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), Institut de Biologie et de Technologies de Saclay ( IBITECS ), Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), University College of London [London] ( UCL ), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés ( LISBP ), Institut National de la Recherche Agronomique ( INRA ) -Institut National des Sciences Appliquées - Toulouse ( INSA Toulouse ), and Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
Iron-Sulfur Proteins, Hydrogenase, Coordination sphere, Protein Conformation, General Chemical Engineering, Phenylalanine, Oxidative phosphorylation, Hydrogenase mimic, Photochemistry, Electrocatalyst, [ CHIM ] Chemical Sciences, Catalysis, Oxidizing agent, [CHIM]Chemical Sciences, chemistry.chemical_classification, General Chemistry, Combinatorial chemistry, Kinetics, Enzyme, chemistry, Mutation, Enzyme mechanisms, Tyrosine, hydrogenases, hydrogen, density functional theory, molecular dynamics, Electrocatalysis, Oxidation-Reduction, Hydrogen
Abstract

Nature is a valuable source of inspiration in the design of catalysts, and various approaches are used to elucidate the mechanism of hydrogenases, the enzymes that oxidize or produce H 2. In FeFe hydrogenases, H 2 oxidation occurs at the H-cluster, and catalysis involves H 2 binding on the vacant coordination site of an iron centre. Here, we show that the reversible oxidative inactivation of this enzyme results from the binding of H 2 to coordination positions that are normally blocked by intrinsic CO ligands. This flexibility of the coordination sphere around the reactive iron centre confers on the enzyme the ability to avoid harmful reactions under oxidizing conditions, including exposure to O 2. The versatile chemistry of the diiron cluster in the natural system might inspire the design of novel synthetic catalysts for H 2 oxidation. © 2014 Macmillan Publishers Limited.

Published
2014
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4. Uncovering a Dynamically Formed Substrate Access Tunnel in Carbon Monoxide Dehydrogenase/Acetyl-CoA Synthase

Author

Luca De Gioia, Jochen Blumberger, Maurizio Bruschi, Po-hung Wang, Wang, P, Bruschi, M, DE GIOIA, L, and Blumberger, J

Subjects
Models, Molecular, Enzyme complex, Ligand Migration, Stereochemistry, Protein subunit, Acetate-CoA Ligase, Molecular Dynamics Simulation, Biochemistry, Catalysis, Substrate Specificity, Enzyme catalysis, Colloid and Surface Chemistry, Multienzyme Complexes, Molecular-Dynamic, Metal Center, Carbon Monoxide, biology, Active-Site, Ligand, Chemistry, Myoglobin, Active site, Substrate (chemistry), General Chemistry, Clostridium-Thermoaceticum, Carbon Dioxide, Aldehyde Oxidoreductases, Acetyl-CoA, biology.protein, Quantum Theory, Chemical binding, Simulation, Carbon monoxide dehydrogenase, Diffusion-Coefficient
Abstract

The transport of small ligands to active sites of proteins is the basis of vital processes in biology such as enzymatic catalysis and cell signaling, but also of more destructive ones including enzyme inhibition and oxidative damage. Here, we show how a diffusion-reaction model solved by means of molecular dynamics and density functional theory calculations provides novel insight into the transport of small ligands in proteins. In particular, we unravel the existence of an elusive, dynamically formed gas channel, which CO2 takes to diffuse from the solvent to the active site (C-cluster) of the bifunctional multisubunit enzyme complex carbon monoxide dehydrogenase/acetyl-CoA synthase (CODH/ACS). Two cavities forming this channel are temporarily created by protein fluctuations and are not apparent in the X-ray structures. The ligand transport is controlled by two residues at the end of this tunnel, His113 and His116, and occurs on the same time scale on which chemical binding to the active site takes place (0.1-1 ms), resulting in an overall binding rate on the second time scale. We find that upon reduction of CO2 to CO, the newly formed Fe-hydroxy ligand greatly strengthens the hydrogen-bond network, preventing CO from exiting the protein through the same way that CO2 takes to enter the protein. This is the basis for directional transport of CO from the production site (C-cluster of CODH subunit) to the utilization site (A-cluster of ACS subunit). In view of these results, a general picture emerges of how large proteins guide small ligands toward their active sites.

Published
2013

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