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  • 1.
    Amrein, Beat A.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structure and Molecular Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bauer, Paul
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structure and Molecular Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Duarte, Fernanda
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structure and Molecular Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Janfalk Carlsson, Åsa
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry.
    Naworyta, Agata
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mowbray, Sherry L.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structure and Molecular Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Widersten, Mikael
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry.
    Kamerlin, Shina C. L.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structure and Molecular Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Expanding the catalytic triad in epoxide hydrolases and related enzymes2015In: ACS Catalysis, ISSN 2155-5435, E-ISSN 2155-5435, Vol. 5, no 10, p. 5702-5713Article in journal (Refereed)
    Abstract [en]

    Potato epoxide hydrolase 1 exhibits rich enantio- and regioselectivity in the hydrolysis of a broadrange of substrates. The enzyme can be engineered to increase the yield of optically pureproducts, as a result of changes in both enantio- and regioselectivity. It is thus highly attractive inbiocatalysis, particularly for the generation of enantiopure fine chemicals and pharmaceuticals.The present work aims to establish the principles underlying the activity and selectivity of theenzyme through a combined computational, structural, and kinetic study, using the substratetrans-stilbene oxide as a model system. Extensive empirical valence bond simulations have beenperformed on the wild-type enzyme together with several experimentally characterized mutants.We are able to computationally reproduce the differences in activities between differentstereoisomers of the substrate, and the effects of mutations in several active-site residues. Inaddition, our results indicate the involvement of a previously neglected residue, H104, which iselectrostatically linked to the general base, H300. We find that this residue, which is highlyconserved in epoxide hydrolases and related hydrolytic enzymes, needs to be in its protonatedform in order to provide charge balance in an otherwise negatively-charged active site. Our datashow that unless the active-site charge balance is correctly treated in simulations, it is notpossible to generate a physically meaningful model for the enzyme that can accurately reproduceactivity and selectivity trends. We also expand our understanding of other catalytic residues,demonstrating in particular the role of a non-canonical residue, E35, as a “backup-base” in theabsence of H300. Our results provide a detailed view of the main factors driving catalysis andregioselectivity in this enzyme, and identify targets for subsequent enzyme design efforts.

  • 2.
    Aqvist, Johan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Kamerlin, Shina C. L.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Conserved Motifs in Different Classes of GTPases Dictate their Specific Modes of Catalysis2016In: ACS Catalysis, ISSN 2155-5435, E-ISSN 2155-5435, Vol. 6, no 3, p. 1737-1743Article in journal (Refereed)
    Abstract [en]

    The GTPase superfamily of enzymes that hydrolyze GTP have a number of conserved sequence regions (the so-called "G-motifs"), and several of the subfamilies also require catalytic activation by specific GTPase-activating proteins. In the translational GTPases involved in protein synthesis, this activating function is instead accomplished by their interaction with the ribosome. Despite these similarities, there are distinct differences regarding some of the amino acid residues making up the GTPase active sites. This raises the question of whether or not the catalytic mechanisms of different types of GTPases are identical. We report herein extensive computer simulations of both the intrinsic GTP hydrolysis reaction of Ras and the considerably faster reaction activated by the interaction with RasGAP. The results of these calculations are compared to earlier simulations of GTP hydrolysis by EF-Tu on the ribosome and show that the favored reaction pathways are strongly dependent on the composition of the active site. By computing Arrhenius plots for the temperature dependence of the calculated free energy profiles, we further show that different mechanistic pathways are associated with distinct differences in activation entropies and enthalpies. The activation parameters are in good agreement with experimental data, and we conclude that calculations of Arrhenius plots from computer simulations can be very useful for dissecting the energetics of enzyme catalysis.

  • 3.
    Cortina, George A.
    et al.
    Univ Virginia, Dept Mol Physiol & Biol Phys, Box 800886, Charlottesville, VA 22908 USA;Univ Virginia, Dept Biomed Engn, Box 800886, Charlottesville, VA 22908 USA.
    Hays, Jennifer M.
    Univ Virginia, Dept Mol Physiol & Biol Phys, Box 800886, Charlottesville, VA 22908 USA;Univ Virginia, Dept Biomed Engn, Box 800886, Charlottesville, VA 22908 USA.
    Kasson, P. M.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics. Uppsala University, Science for Life Laboratory, SciLifeLab. Univ Virginia, Dept Mol Physiol & Biol Phys, Box 800886, Charlottesville, VA 22908 USA;Univ Virginia, Dept Biomed Engn, Box 800886, Charlottesville, VA 22908 USA.
    Conformational Intermediate That Controls KPC-2 Catalysis and Beta-Lactam Drug Resistance2018In: ACS Catalysis, ISSN 2155-5435, E-ISSN 2155-5435, Vol. 8, no 4, p. 2741-2747Article in journal (Refereed)
    Abstract [en]

    The KPC-2 carbapenemase enzyme is responsible for drug resistance in the majority of carbapenem-resistant Gram-negative bacterial infections in the United States. A better understanding of what permits KPC-2 to hydrolyze carbapenem antibiotics and how this might be inhibited is thus of fundamental interest and great practical importance to development of better anti-infectives. By correlating molecular dynamics simulations with experimental enzyme kinetics, we identified conformational changes that control KPC-2's ability to hydrolyze carbapenem antibiotics. Related beta-lactamase enzymes can interconvert between catalytically permissive and catalytically nonpermissive forms of an acylenzyme intermediate critical to drug hydrolysis. identify a similar equilibrium in KPC-2 and analyze the determinants of this conformational change. Because the conformational dynamics of KPC-2 are complex and sensitive to allosteric changes, we develop an information-theoretic approach to identify key determinants of this change. We measure unbiased estimators of the reaction coordinate between catalytically permissive and nonpermissive states, perform information-theoretic feature selection, and, using restrained molecular dynamics simulations, validate the protein conformational changes predicted to control catalytically permissive geometry. We identify two binding pocket residues that control the conformational transitions between catalytically active and inactive forms of KPC-2. Mutations to one of these residues, Trp105, lower the stability of the catalytically permissive state in simulations and have reduced experimental k(cat) values that show a strong linear correlation with the simulated catalytically permissive state lifetimes. This understanding can be leveraged to predict the drug resistance of further KPC-2 mutants and help design inhibitors to combat extreme drug resistance.

  • 4.
    Daniel, Quentin
    et al.
    KTH Royal Inst Technol, Sch Chem Sci & Engn, Dept Chem, S-10044 Stockholm, Sweden..
    Anabre, Ram B.
    KTH Royal Inst Technol, Sch Chem Sci & Engn, Dept Chem, S-10044 Stockholm, Sweden..
    Zhang, Biaobiao
    KTH Royal Inst Technol, Sch Chem Sci & Engn, Dept Chem, S-10044 Stockholm, Sweden..
    Philippe, Bertrand
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Molecular and Condensed Matter Physics.
    Chen, Hong
    KTH Royal Inst Technol, Sch Chem Sci & Engn, Dept Chem, S-10044 Stockholm, Sweden..
    Li, Fusheng
    KTH Royal Inst Technol, Sch Chem Sci & Engn, Dept Chem, S-10044 Stockholm, Sweden..
    Fan, Ke
    KTH Royal Inst Technol, Sch Chem Sci & Engn, Dept Chem, S-10044 Stockholm, Sweden..
    Ahmadi, Sareh
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Molecular and Condensed Matter Physics.
    Rensmo, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Molecular and Condensed Matter Physics.
    Sun, Licheng
    KTH Royal Inst Technol, Sch Chem Sci & Engn, Dept Chem, S-10044 Stockholm, Sweden.;Dalian Univ Technol, State Key Lab Fine Chem, DUT KTH Joint Educ & Res Ctr Mol Devices, Dalian 116024, Peoples R China..
    Re-Investigation of Cobalt Porphyrin for Electrochemical Water Oxidation on FTO Surface: Formation of CoOx as Active Species2017In: ACS Catalysis, ISSN 2155-5435, E-ISSN 2155-5435, Vol. 7, no 2, p. 1143-1149Article in journal (Refereed)
    Abstract [en]

    The use of cobalt porphyrin complexes as efficient and cost-effective molecular catalysts for water oxidation has been investigated previously. However, by combining a set of analytical techniques (electrochemistry, ultraviolet-visible spectroscopy (UV-vis), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and synchrotron-based photoelectron spectroscopy (SOXPES and HAXPES)), we have demonstrated that three different cobalt porphyrins, deposited on FTO glasses, decompose promptly into a thin film of CoOx on the surface of the electrode during water oxidation under certain conditions (borate buffer pH 9.2). It is presumed that the film is composed of CoO, only detectable by SOXPES, as conventional techniques are ineffective. This newly formed film has a high turnover frequency (TOF), while the high transparency of the CoOx-based electrode is very promising for future application in photoelectrochemical cells.

  • 5.
    Fan, Ting
    et al.
    KTH Royal Inst Technol, Sch Biotechnol, Div Theoret Chem & Biol, S-10691 Stockholm, Sweden..
    Duan, Lele
    KTH Royal Inst Technol, Dept Chem, S-10044 Stockholm, Sweden.;Southern Univ Sci & Technol, Dept Chem, Shenzhen 518055, Peoples R China..
    Huang, Ping
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Chen, Hong
    KTH Royal Inst Technol, Dept Chem, S-10044 Stockholm, Sweden..
    Daniel, Quentin
    KTH Royal Inst Technol, Dept Chem, S-10044 Stockholm, Sweden..
    Ahlquist, Marten S. G.
    KTH Royal Inst Technol, Sch Biotechnol, Div Theoret Chem & Biol, S-10691 Stockholm, Sweden..
    Sun, Licheng
    KTH Royal Inst Technol, Dept Chem, S-10044 Stockholm, Sweden.;Dalian Univ Technol, DUT KTH Joint Educ & Res Ctr Mol Devices, State Key Lab Fine Chem, Dalian 116012, Peoples R China..
    The Ru-tpc Water Oxidation Catalyst and Beyond: Water Nucleophilic Attack Pathway versus Radical Coupling Pathway.2017In: ACS Catalysis, ISSN 2155-5435, E-ISSN 2155-5435, Vol. 7, no 4, p. 2956-2966Article in journal (Refereed)
    Abstract [en]

    Many Ru water oxidation catalysts have been documented in the literature. However, only a few can catalyze the O-O bond formation via the radical coupling pathway, while most go through the water nucleophilic attack pathway. Understanding the electronic effect on the reaction pathway is of importance in design of active water oxidation catalysts. The Ru-bda (bda = 2,2'-bipyridine-6,6'-dicarboxylate) catalyst is one example that catalyzes the 0-0 bond formation via the radical coupling pathway. Herein, we manipulate the equatorial backbone ligand, change the doubly charged bda(2-) ligand to a singly charged tpc- (2,2':6',2 ''-terpyridine-6-carboxylate) ligand, and study the structure activity relationship. Surprisingly, kinetics measurements revealed that the resulting Ru-tpc catalyst catalyzes water oxidation via the water nucleophilic attack pathway, which is different from the Ru-bda catalyst. The O-O bond formation Gibbs free energy of activation (AGO) at T = 298.15 K was 20.2 +/- 1.7 kcal mol(-1). The electronic structures of a series of Ru-v=O species were studied by density function theory calculations, revealing that the spin density of O-Ru=O of Ru-v=O is largely dependent on the surrounding ligands. Seven coordination configuration significantly enhances the radical character of Ru-v=O.

  • 6.
    Guha, Anku
    et al.
    Tata Inst Fundamental Res Hyderabad, Sy 36-P, Hyderabad 500107, India.
    Vineesh, Thazhe Veettil
    Tata Inst Fundamental Res Hyderabad, Sy 36-P, Hyderabad 500107, India.
    Sekar, Archana
    Tata Inst Fundamental Res Hyderabad, Sy 36-P, Hyderabad 500107, India.
    Narayanaru, Sreekanth
    Tata Inst Fundamental Res Hyderabad, Sy 36-P, Hyderabad 500107, India.
    Sahoo, Mihir
    Indian Inst Technol, Sch Basic Sci, Bhubaneswar 751013, Odisha, India.
    Nayak, Saroj
    Indian Inst Technol, Sch Basic Sci, Bhubaneswar 751013, Odisha, India.
    Chakraborty, Sudip
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Narayanan, Tharangattu N.
    Tata Inst Fundamental Res Hyderabad, Sy 36-P, Hyderabad 500107, India.
    Mechanistic Insight into Enhanced Hydrogen Evolution Reaction Activity of Ultrathin Hexagonal Boron Nitride-Modified Pt Electrodes2018In: ACS Catalysis, ISSN 2155-5435, E-ISSN 2155-5435, Vol. 8, no 7, p. 6636-6644Article in journal (Refereed)
    Abstract [en]

    Enhancing the intrinsic activity of a benchmarked electrocatalyst such as platinum (Pt) is highly intriguing from fundamental as well as applied perspectives. In this work, hydrogen evolution reaction (HER) activity of Pt electrodes, benchmarked HER catalysts, modified with ultrathin sheets of hexagonal boron nitride (h-BN) is studied in acidic medium (Pt/h-BN), and augmented HER performance, in terms of the overpotential at a 10 mA cm(-2) current density (10 mV lower than that of Pt nanoparticles) and a lower Tafel slope (29 +/- 1 mV/decade), of the Pt/h-BN system is demonstrated. The effects of h-BN surface modification of bulk Pt as well as Pt nanoparticles are studied, and the origin of such an enhanced HER activity is probed using density functional theory-based calculations. The HER charge transfer resistance of h-BN-modified Pt is found to be drastically reduced, and this enhances the charge transfer kinetics of the Pt/h-BN system because of the synergistic interaction between h-BN and Pt. An enormous reduction in the hydrogen adsorption energy on h-BN monolayers is also found when they are placed over the Pt electrode [-2.51 eV (h-BN) to -0.25 eV (h-BN over Pt)]. Corrosion preventive atomic layers such as h-BN-protected Pt electrodes that perform better than Pt electrodes do open possibilities of benchmarked catalysts by simple modification of a surface via atomic layers.

  • 7. Kartusch, Christiane
    et al.
    Krumeich, Frank
    Safonova, Olga
    Hartfelder, Urs
    Makosch, Martin
    Sa, Jacinto
    van Bokhoven, Jeroen A.
    Redispersion of Gold Multiple-Twinned Particles during Liquid-Phase Hydrogenation2012In: ACS Catalysis, ISSN 2155-5435, E-ISSN 2155-5435, Vol. 2, no 7, p. 1394-1403Article in journal (Refereed)
  • 8.
    Kazemi, Masoud
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics.
    Himo, Fahmi
    Stockholm Univ, Arrhenius Lab, Dept Organ Chem, SE-10691 Stockholm, Sweden..
    Åqvist, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics.
    Peptide Release on the Ribosome Involves Substrate-Assisted Base Catalysis2016In: ACS Catalysis, ISSN 2155-5435, E-ISSN 2155-5435, Vol. 6, no 12, p. 8432-8439Article in journal (Refereed)
    Abstract [en]

    Termination of protein synthesis on the ribosome involves hydrolysis of the ester bond between the P-site tRNA and the nascent peptide chain. This reaction occurs in the peptidyl transferase center and is triggered by the class I release factors RF1 and RF2 in prokaryotes. Peptidyl-tRNA hydrolysis is pH-dependent, and experimental results suggest that an ionizable group with pK(a) > 9 is involved in the reaction. The nature of this group is, however, unknown. To resolve this problem, we conducted density functional theory calculations using a large cluster model of the peptidyl transferase center. Our calculations reveal that peptidyl-tRNA hydrolysis occurs via a base-catalyzed mechanism with a predicted activation energy of 15.8 kcal mol(-1), which is in good agreement with experimental data. In this mechanism, the P-site A76 2'-OH group is deprotonated and acts as the general base by activating the nucleophilic water molecule. The energy cost of deprotonating the 2'-hydroxyl group at pH 7.5 is estimated to be about 8 kcal mo1(-1), on the basis of its experimental plc in aqueous solution, and this step is predicted to be the source of the observed pH dependence. The proposed mechanism is consistent not only with experimentally derived activation energies but also with the observed kinetic solvent isotope effect.

  • 9. Makosch, Martin
    et al.
    Lin, Wan-Ing
    Bumbalek, Viclav
    Sa, Jacinto
    Medlin, J. Will
    Hungerbuehler, Konrad
    van Bokhoven, Jeroen A.
    Organic Thiol Modified Pt/TiO2 Catalysts to Control Chemoselective Hydrogenation of Substituted Nitroarenes2012In: ACS Catalysis, ISSN 2155-5435, E-ISSN 2155-5435, Vol. 2, no 10, p. 2079-2081Article in journal (Refereed)
  • 10.
    Marcos, Rocio
    et al.
    KTH Royal Inst Technol, Div Theoret Chem & Biol, Sch Biotechnol, SE-10691 Stockholm, Sweden..
    Xue, Liqin
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Theoretical Chemistry. KTH Royal Inst Technol, Div Theoret Chem & Biol, Sch Biotechnol, SE-10691 Stockholm, Sweden..
    Sanchez-de-Armas, Rocio
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory. KTH Royal Inst Technol, Div Theoret Chem & Biol, Sch Biotechnol, SE-10691 Stockholm, Sweden..
    Ahlquist, Marten S. G.
    KTH Royal Inst Technol, Div Theoret Chem & Biol, Sch Biotechnol, SE-10691 Stockholm, Sweden..
    Bicarbonate Hydrogenation Catalyzed by Iron: How the Choice of Solvent Can Reverse the Reaction2016In: ACS Catalysis, ISSN 2155-5435, E-ISSN 2155-5435, Vol. 6, no 5, p. 2923-2929Article in journal (Refereed)
    Abstract [en]

    Here we report a mechanism study of the hydrogenation of bicarbonate by tetradentate phosphines iron-complexes. It is an extension of our recent study on the reverse reaction by the same type of complexes [Chem.-Eur. J. 2013, 19, 11869], with special emphasis herein on the effects of the choice of solvent. By using density functional theory we have located the most plausible mechanism and have found remarkable effects of the solvent on the reversibility of this reaction. We predict that the solvent used in experiment, MeOH, for the hydrogenation of bicarbonate to formate could be replaced to enhance the activity of the system. There is a direct correlation of the solubility of the base to favor or disfavor the hydrogenation of bicarbonate to formate.

  • 11.
    Maurer, Dirk
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Enugala, Thilak Reddy
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry.
    Hamnevik, Emil
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Bauer, Paul
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Molecular Cell Biology.
    Lüking, Malin
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Petrovic, Dusan
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Hillier, Heidi
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström.
    Kamerlin, Shina C. L.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Dobritzsch, Doreen
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry.
    Widersten, Mikael
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry.
    Stereo- and Regioselectivity in Catalyzed Transformation of a 1,2-Disubstituted Vicinal Diol and the Corresponding Diketone by Wild Type and Laboratory Evolved Alcohol Dehydrogenases2018In: ACS Catalysis, ISSN 2155-5435, E-ISSN 2155-5435, Vol. 8, no 8, p. 7526-7538Article in journal (Refereed)
    Abstract [en]

    ADH-A from Rhodococcus ruber DSM 44541 catalyzes the oxidation of (S)-1-phenylethanol 3000-fold more efficiently as compared with the 2-hydroxylated derivative (R)-phenylethane-1,2-diol. The enzyme is also highly selective for sec-alcohols with comparably low activities with the corresponding primary alcohols. When challenged with a substrate containing two secondary alcohols, such as 1-phenylpropane-(1R,2S)-diol, ADH-A favors the oxidation of the benzylic carbon of this alcohol. The catalytic efficiency, however, is modest in comparison to the activity with (S)-1-phenylethanol. To investigate the structural requirements for improved oxidation of vicinal diols, we conducted iterative saturation mutagenesis combined with activity screening. A first-generation variant, B1 (Y54G, L119Y) displays a 2-fold higher kcat value with 1-phenylpropane-(1R,2S)-diol and a shift in the cooperative behavior in alcohol binding, from negative in the wild type, to positive in B1, suggesting a shift from a less active enzyme form (T) in the wild type to a more active form (R) in the B1 variant. Also, the regiopreference changed to favor oxidation of C-2. A second-generation variant, B1F4 (F43T, Y54G, L119Y, F282W), shows further improvement in the turnover and regioselectivity in oxidation of 1-phenylpropane-(1R,2S)-diol. The crystal structures of the B1 and B1F4 variants describe the structural alterations to the active site, the most significant of which is a repositioning of a Tyr side-chain located distal to the coenzyme and the catalytic zinc ion. The links between the changes in structures and stereoselectivities are rationalized by molecular dynamics simulations of substrate binding at the respective active sites.

    Keywords: alcohol dehydrogenase; alcohol oxidation; biocatalysis; crystal structure; directed evolution; enzyme engineering; molecular dynamics simulations; stereoselectivity

  • 12.
    Pasti, Igor A.
    et al.
    Univ Belgrade, Fac Phys Chem, Belgrade, Serbia; KTH Royal Inst Technol, Sch Ind Engn & Management, Dept Mat Sci & Engn, Stockholm, Sweden.
    Fako, Edvin
    Barcelona Inst Sci & Technol, Inst Chem Res Catalonia ICIQ, Tarragona, Spain.
    Dobrota, Ana S.
    Univ Belgrade, Fac Phys Chem, Belgrade, Serbia.
    Lopez, Nuria
    Barcelona Inst Sci & Technol, Inst Chem Res Catalonia ICIQ, Tarragona, Spain.
    Skorodumova, Natalia V.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory. KTH Royal Inst Technol, Sch Ind Engn & Management, Dept Mat Sci & Engn, Stockholm, Sweden.
    Mentus, Slavko V.
    Univ Belgrade, Fac Phys Chem, Belgrade, Serbia; Serbian Acad Arts & Sci, Belgrade, Serbia.
    Atomically Thin Metal Films on Foreign Substrates: From Lattice Mismatch to Electrocatalytic Activity2019In: ACS Catalysis, ISSN 2155-5435, E-ISSN 2155-5435, Vol. 9, no 4, p. 3467-3481Article in journal (Refereed)
    Abstract [en]

    Electrocatalytic properties of materials are governed by the electronic structure, stability, and reactivity of the surface layer which is exposed to the electrolyte. Over the years, different strategies have been developed to tailor electrocatalyst surfaces but also to reduce the cost of these materials, which is the bottleneck for any practical application. When a very thin metallic layer, intended to serve as an electrocatalyst, is placed over a substrate, its configuration is influenced by the structure of the substrate due to lattice mismatch, while the electronic structure is affected due to the strain and the electronic effects of the support. This results in altered bonding within the electrocatalyst layer and the modification of its electronic properties when compared to the pure phase. In this contribution, we address the possibilities of theoretical prediction of surface properties of atomically thin electrocatalyst films formed over different substrates, focusing on the metal side of the electrified interface. While all these properties can be calculated quite easily using modern computational techniques (but used with care), most often based on density functional theory, we also address an attractive, fast screening possibility to estimate the properties of monometallic and multimetallic overlayers using small sets of calculations on model systems. We discuss how lattice mismatch between a substrate and an overlayer can be used to predict the properties of electrocatalytic films, limitations of such approach, and a possibility of deploying of large databases which enable rapid prescreening of different support/overlayer systems for various electrocatalytic applications.

  • 13.
    Petrovic, Dusan
    et al.
    Forschungszentrum Julich, Inst Complex Syst Struct Biochem, D-52425 Julich, Germany..
    Frank, David
    Rhein Westfal TH Aachen, Inst Mol Biotechnol, Worringerweg 1, D-52074 Aachen, Germany.;Aquila Biolabs GmbH, Arnold Sommerfeld Ring 2, D-52499 Baesweiler, Germany..
    Kamerlin, Shina C. Lynn
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structure and Molecular Biology.
    Hoffmann, Kurt
    Rhein Westfal TH Aachen, Inst Mol Biotechnol, Worringerweg 1, D-52074 Aachen, Germany..
    Strodel, Birgit
    Forschungszentrum Julich, Inst Complex Syst Struct Biochem, D-52425 Julich, Germany.;Heinrich Heine Univ Dusseldorf, Inst Theoret & Computat Chem, Univ Str 1, D-40225 Dusseldorf, Germany..
    Shuffling Active Site Substate Populations Affects Catalytic Activity: The Case of Glucose Oxidase2017In: ACS Catalysis, ISSN 2155-5435, E-ISSN 2155-5435, Vol. 7, no 9, p. 6188-6197Article in journal (Refereed)
    Abstract [en]

    Glucose oxidase has wide applications in the pharmaceutical, chemical, and food industries. Many recent studies have enhanced key properties of this enzyme using directed evolution, yet without being able to reveal why these mutations are actually beneficial. This work presents a synergistic combination of experimental and computational methods, indicating how mutations, even when distant from the active site, positively affect glucose oxidase catalysis. We have determined the crystal structures of glucose oxidase mutants containing molecular oxygen in the active site. The catalytically important His516 residue has been previously shown to be flexible in the wild-type enzyme. The molecular dynamics simulations performed in this work allow us to quantify this floppiness, revealing that His516 exists in two states: catalytic and noncatalytic. The relative populations of these two substates are almost identical in the wild-type enzyme, with His516 readily shuffling between them. In the glucose oxidase mutants, on the other hand, the mutations enrich the catalytic His516 conformation and reduce the flexibility of this residue, leading to an enhancement in their catalytic efficiency. This study stresses the benefit of active site preorganization with respect to enzyme conversion rates by reducing molecular reorientation needs. We further suggest that the computational approach based on Hamiltonian replica exchange molecular dynamics, used in this study, may be a general approach to screening in silico for improved enzyme variants involving flexible catalytic residues.

  • 14. Sa, Jacinto
    et al.
    Taylor, Sarah Frances Rebecca
    Daly, Helen
    Goguet, Alexandre
    Tiruvalam, Ramchandra
    He, Qian
    Kiely, Christopher J.
    Hutchings, Graham J.
    Hardacre, Christopher
    Redispersion of Gold Supported on Oxides2012In: ACS Catalysis, ISSN 2155-5435, E-ISSN 2155-5435, Vol. 2, no 4, p. 552-560Article in journal (Refereed)
  • 15.
    Uduwela, Dimanthi R.
    et al.
    Australian Natl Univ, Res Sch Chem, Canberra, ACT 2601, Australia.
    Pabis, Anna
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
    Stevenson, Bradley J.
    Australian Natl Univ, Res Sch Chem, Canberra, ACT 2601, Australia.
    Kamerlin, Shina C. Lynn
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structural Biology.
    McLeod, Malcolm D.
    Australian Natl Univ, Res Sch Chem, Canberra, ACT 2601, Australia.
    Enhancing the Steroid Sulfatase Activity of the Arylsulfatase from Pseudomonas aeruginosa2018In: ACS Catalysis, ISSN 2155-5435, E-ISSN 2155-5435, Vol. 8, no 9, p. 8902-8914Article in journal (Refereed)
    Abstract [en]

    Steroidal sulfate esters play a central role in many physiological processes. They serve as the reservoir for endogenous sex hormones and form a significant fraction of the steroid metabolite pool. The analysis of steroid sulfates is thus essential in fields such as medical science and sports drug testing. Although the direct detection of steroid sulfates can be readily achieved using liquid chromatography-mass spectrometry, many analytical approaches, including gas chromatography-mass spectrometry, are hampered due to the lack of suitable enzymatic or chemical methods for sulfate ester hydrolysis prior to analysis. Enhanced methods of steroid sulfate hydrolysis would expand analytical possibilities for the study of these widely occurring metabolites. The arylsulfatase from Pseudomonas aeruginosa (PaS) is a purified enzyme capable of hydrolyzing steroid sulfates. However, this enzyme requires improvement to hydrolytic activity and substrate scope in order to be useful in analytical applications. These improvements were sought by applying semirational design to mutate amino acid residues neighboring the enzyme active site. Mutagenesis was implemented on both single and multiple residue sites. Screening by ultra-high performance liquid chromatography-mass spectrometry was performed to test the steroid sulfate hydrolysis activity of these mutant libraries against testosterone sulfate. This approach revealed the steroid sulfate binding pocket and resulted in three mutants that showed an improvement in catalytic efficiency (V-max/K-M) of more than 150 times that of wild-type PaS. The substrate scope of PaS was expanded, and a modest increase in thermostability was observed. Finally, molecular dynamics simulations of enzyme-substrate complexes were used to provide qualitative insight into the structural origin of the observed effects.

  • 16. Zhang, Biaobiao
    et al.
    Chen, Hong
    Daniel, Quentin
    Philippe, Bertrand
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Molecular and Condensed Matter Physics.
    Yu, Fengshou
    Valvo, Mario
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Structural Chemistry.
    Li, Yuanyuan
    Ambre, Ram B.
    Zhang, Peili
    Li, Fei
    Rensmo, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Molecular and Condensed Matter Physics.
    Sun, Licheng
    Defective and “c-Disordered” Hortensia-like Layered MnOx as an Efficient Electrocatalyst for Water Oxidation at Neutral pH2017In: ACS Catalysis, ISSN 2155-5435, E-ISSN 2155-5435, Vol. 7, no 9, p. 6311-6322Article in journal (Refereed)
    Abstract [en]

    The development of a highly active manganese-based water oxidation catalyst in the design of an ideal artificial photosynthetic device operating under neutral pH conditions remains a great challenge, due to the instability of pivotal Mn3+ intermediates. We report here defective and “c-disordered” layered manganese oxides (MnOx-300) formed on a fluorine-doped tin oxide electrode by constant anodic potential deposition and subsequent annealing, with a catalytic onset (0.25 mA/cm2) at an overpotential (η) of 280 mV and a benchmark catalytic current density of 1.0 mA/cm2 at an overpotential (η) of 330 mV under neutral pH (1 M potassium phosphate). Steady current density above 8.2 mA/cm2 was obtained during the electrolysis at 1.4 V versus the normal hydrogen electrode for 20 h. Insightful studies showed that the main contributing factors for the observed high activity of MnOx-300 are (i) a defective and randomly stacked layered structure, (ii) an increased degree of Jahn–Teller distorted Mn3+ in the MnO6 octahedral sheets, (iii) effective stabilization of Mn3+, (iv) a high surface area, and (v) improved electrical conductivity. These results demonstrate that manganese oxides as structural and functional models of an oxygen-evolving complex (OEC) in photosystem II are promising catalysts for water oxidation in addition to Ni/Co-based oxides/hydroxides.

1 - 16 of 16
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