The Experts below are selected from a list of 12714 Experts worldwide ranked by ideXlab platform
Stephen J Lippard - One of the best experts on this subject based on the ideXlab platform.
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tracking a defined route for o2 migration in a Dioxygen activating diiron enzyme
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Woon Ju Song, Grant C Gucinski, Matthew H Sazinsky, Stephen J LippardAbstract:For numerous enzymes reactive toward small gaseous compounds, growing evidence indicates that these substrates diffuse into active site pockets through defined pathways in the protein matrix. Toluene/o-xylene monooxygenase hydroxylase is a Dioxygen-activating enzyme. Structural analysis suggests two possible pathways for Dioxygen access through the α-subunit to the diiron center: a channel or a series of hydrophobic cavities. To distinguish which is utilized as the O2 migration pathway, the dimensions of the cavities and the channel were independently varied by site-directed mutagenesis and confirmed by X-ray crystallography. The rate constants for Dioxygen access to the diiron center were derived from the formation rates of a peroxodiiron(III) intermediate, generated upon treatment of the diiron(II) enzyme with O2. This reaction depends on the concentration of Dioxygen to the first order. Altering the dimensions of the cavities, but not the channel, changed the rate of Dioxygen reactivity with the enzyme. These results strongly suggest that voids comprising the cavities in toluene/o-xylene monooxygenase hydroxylase are not artifacts of protein packing/folding, but rather programmed routes for Dioxygen migration through the protein matrix. Because the cavities are not fully connected into the diiron active center in the enzyme resting state, conformational changes will be required to facilitate Dioxygen access to the diiron center. We propose that such temporary opening and closing of the cavities may occur in all bacterial multicomponent monooxygenases to control O2 consumption for efficient catalysis. Our findings suggest that other gas-utilizing enzymes may employ similar structural features to effect substrate passage through a protein matrix.
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how iron containing proteins control Dioxygen chemistry a detailed atomic level description via accurate quantum chemical and mixed quantum mechanics molecular mechanics calculations
Coordination Chemistry Reviews, 2003Co-Authors: Richard A Friesner, Benjamin F. Gherman, Victor Guallar, Muhyun Baik, Maria E Wirstam, Robert B Murphy, Stephen J LippardAbstract:Abstract Over the past several years, rapid advances in computational hardware, quantum chemical methods, and mixed quantum mechanics/molecular mechanics (QM/MM) techniques have made it possible to model accurately the interaction of ligands with metal-containing proteins at an atomic level of detail. In this paper, we describe the application of our computational methodology, based on density functional (DFT) quantum chemical methods, to two diiron-containing proteins that interact with Dioxygen: methane monooxygenase (MMO) and hemerythrin (Hr). Although the active sites are structurally related, the biological function differs substantially. MMO is an enzyme found in methanotrophic bacteria and hydroxylates aliphatic C–H bonds, whereas Hr is a carrier protein for Dioxygen used by a number of marine invertebrates. Quantitative descriptions of the structures and energetics of key intermediates and transition states involved in the reaction with Dioxygen are provided, allowing their mechanisms to be compared and contrasted in detail. An in-depth understanding of how the chemical identity of the first ligand coordination shell, structural features, electrostatic and van der Waals interactions of more distant shells control ligand binding and reactive chemistry is provided, affording a systematic analysis of how iron-containing proteins process Dioxygen. Extensive contact with experiment is made in both systems, and a remarkable degree of accuracy and robustness of the calculations is obtained from both a qualitative and quantitative perspective.
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reactions of nitric oxide with the reduced non heme diiron center of the soluble methane monooxygenase hydroxylase
Biochemistry, 1999Co-Authors: David E Coufal, Pedro Tavares, Alice S Pereira, Boi Hanh Hyunh, Stephen J LippardAbstract:The soluble methane monooxygenase system from Methylococcus capsulatus (Bath) catalyzes the oxidation of methane to methanol and water utilizing Dioxygen at a non-heme, carboxylate-bridged diiron center housed in the hydroxylase (H) component. To probe the nature of the reductive activation of Dioxygen in this system, reactions of an analogous molecule, nitric oxide, with the diiron(II) form of the enzyme (Hred) were investigated by both continuous and discontinuous kinetics methodologies using optical, EPR, and Mossbauer spectroscopy. Reaction of NO with Hred affords a dinitrosyl species, designated Hdinitrosyl, with optical spectra (λmax = 450 and 620 nm) and Mossbauer parameters (δ = 0.72 mm/s, ΔEQ = 1.55 mm/s) similar to those of synthetic dinitrosyl analogues and of the dinitrosyl adduct of the reduced ribonucleotide reductase R2 (RNR-R2) protein. The Hdinitrosyl species models features of the Hperoxo intermediate formed in the analogous Dioxygen reaction. In the presence of protein B, Hdinitrosyl bu...
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substrate binding and c h bond activation in the soluble methane monooxygenase hydroxylase
Journal of Biological Inorganic Chemistry, 1998Co-Authors: Douglas A Whittington, Ann M Valentine, Stephen J LippardAbstract:The selective oxidation of CH4 to CH3OH is a conceptually simple, yet functionally difficult, chemical transformation. In nature, this reaction is performed by methane monooxygenases, the soluble class of which employ carboxylate-bridged dinuclear iron centers to activate Dioxygen. The process by which small molecules access the active site of the sMMO hydroxylase, the structures of intermediates in the catalytic reaction cycle, and mechanistic details about the attack on the C–H bond are subjects of intense investigation. In this commentary, we present our current views on exogenous ligand binding and Dioxygen activation at the active site and the mechanism of alkane hydroxylation.
Lawrence Que - One of the best experts on this subject based on the ideXlab platform.
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Dioxygen activation by nonheme iron enzymes with the 2-His-1-carboxylate facial triad that generate high-valent oxoiron oxidants
JBIC Journal of Biological Inorganic Chemistry, 2017Co-Authors: Subhasree Kal, Lawrence QueAbstract:The 2-His-1-carboxylate facial triad is a widely used scaffold to bind the iron center in mononuclear nonheme iron enzymes for activating Dioxygen in a variety of oxidative transformations of metabolic significance. Since the 1990s, over a hundred different iron enzymes have been identified to use this platform. This structural motif consists of two histidines and the side chain carboxylate of an aspartate or a glutamate arranged in a facial array that binds iron(II) at the active site. This triad occupies one face of an iron-centered octahedron and makes the opposite face available for the coordination of O_2 and, in many cases, substrate, allowing the tailoring of the iron-Dioxygen chemistry to carry out a plethora of diverse reactions. Activated Dioxygen-derived species involved in the enzyme mechanisms include iron(III)-superoxo, iron(III)-peroxo, and high-valent iron(IV)-oxo intermediates. In this article, we highlight the major crystallographic, spectroscopic, and mechanistic advances of the past 20 years that have significantly enhanced our understanding of the mechanisms of O_2 activation and the key roles played by iron-based oxidants.
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The 2-His-1-carboxylate facial triad: a versatile platform for Dioxygen activation by mononuclear non-heme iron(II) enzymes
JBIC Journal of Biological Inorganic Chemistry, 2005Co-Authors: Kevin D. Koehntop, Joseph P. Emerson, Lawrence QueAbstract:General knowledge of Dioxygen-activating mononuclear non-heme iron(II) enzymes containing a 2-His-1-carboxylate facial triad has significantly expanded in the last few years, due in large part to the extensive library of crystal structures that is now available. The common structural motif utilized by this enzyme superfamily acts as a platform upon which a wide assortment of substrate transformations are catalyzed. The facial triad binds a divalent metal ion at the active site, which leaves the opposite face of the octahedron available to coordinate a variety of exogenous ligands. The binding of substrate activates the metal center for attack by Dioxygen, which is subsequently converted to a high-valent iron intermediate, a formidable oxidizing species. Herein, we summarize crystallographic and mechanistic features of this metalloenzyme superfamily, which has enabled the proposal of a common but flexible pathway for Dioxygen activation.
Judith P Klinman - One of the best experts on this subject based on the ideXlab platform.
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binding of Dioxygen to non metal sites in proteins exploration of the importance of binding site size versus hydrophobicity in the copper amine oxidase from hansenula polymorpha
Biochemistry, 2002Co-Authors: Yoshio Goto, Judith P KlinmanAbstract:Copper amine oxidases (CAOs) contain 2,4,5-trihydroxyphenylalanyl quinone (TPQ) and a copper ion in their active sites, catalyzing amine oxidation to aldehyde and ammonia concomitant with the reduction of molecular oxygen to hydrogen peroxide. Kinetic studies on the CAO from bovine serum (BSAO) [Su and Klinman (1999) Biochemistry 37, 12513−12525] and the recent reports on the cobalt substituted form of the enzyme from Hansenula polymorpha (HPAO) [Mills and Klinman (2000) J. Am. Chem. Soc. 122, 9897−9904, and Mills et al. (2002) Biochemistry, 41, 10577−10584] support pre-binding of molecular oxygen prior to a rate-limiting electron transfer from the reduced form of TPQ (p-aminohydroquinone form) to Dioxygen. Although there is significant sequence homology between BSAO and HPAO, kcat/Km(O2) for BSAO under the optimal condition is one order of magnitude lower than that for HPAO. From a comparison of amino acid sequences for BSAO and HPAO, together with the X-ray crystal structure of HPAO, a plausible dioxyge...
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oxygen kinetic isotope effects in soluble methane monooxygenase
Journal of Biological Chemistry, 2001Co-Authors: Shannon S Stahl, Wilson A Francisco, Maarten Merkx, Judith P KlinmanAbstract:Abstract Soluble methane monooxygenase (sMMO) contains a nonheme, carboxylate-bridged diiron site that activates Dioxygen in the catalytic oxidation of hydrocarbon substrates. Oxygen kinetic isotope effects (KIEs) have been determined under steady-state conditions for the sMMO-catalyzed oxidation of CH3CN, a liquid substrate analog. Kinetic studies of the steady-state sMMO reaction revealed a competition between fully coupled oxygenase activity, which produced glycolonitrile (HOCH2CN) and uncoupled oxidase activity that led to water formation. The oxygen KIE was measured independently for both the oxygenase and oxidase reactions, and values of 1.0152 ± 0.0007 and 1.0167 ± 0.0010 were obtained, respectively. The isotope effects and separate Dioxygen binding studies do not support irreversible formation of an enzyme-Dioxygen Michaelis complex. Additional mechanistic implications are discussed in the context of previous data obtained from single turnover and steady-state kinetic studies.
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life as aerobes are there simple rules for activation of Dioxygen by enzymes
Journal of Biological Inorganic Chemistry, 2001Co-Authors: Judith P KlinmanAbstract:Numerous biological systems involve reaction with Dioxygen in the absence of readily accessible spectroscopic signals. We have begun to develop a set of "generic" strategies that will allow us to probe the mechanisms of Dioxygen activation. In particular, we wish to understand the nature of the Dioxygen binding step, the degree to which electron transfer to Dioxygen is rate limiting, whether reactive species accumulate during turnover and, finally, whether proton and electron transfer to Dioxygen occur as coupled processes. Our strategy will be introduced for an enzyme system that uses only an organic cofactor in Dioxygen activation (glucose oxidase). Two key features emerge from studies of glucose oxidase: (1) that formation of the superoxide anion is a major rate-limiting step and (2) that electrostatic stabilization of the superoxide anion plays a key role in catalysis. Similar themes emerge when our protocols are applied to enzymes containing both an active site metal center and an organic cofactor. Finally, enzymes that rely solely on metal centers for substrate functionalization will be discussed. In no instance, thus far, has evidence been found for a direct coupling of proton to electron transfer in the reductive activation of Dioxygen.
Ning Jiao - One of the best experts on this subject based on the ideXlab platform.
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direct tryptophols synthesis from 2 vinylanilines and alkynes via c c triple bond cleavage and Dioxygen activation
Journal of the American Chemical Society, 2016Co-Authors: Tao Shen, Yiqun Zhang, Yufeng Liang, Ning JiaoAbstract:An unexpected metal-free C≡C triple bond cleavage, Dioxygen activation, and reassembly into tryptophol derivatives has been developed. This chemistry provides a novel, simple, and efficient approach to highly valuable tryptophol derivatives from simple substrates under mild conditions. The mechanistic studies may promote the discovery of new methodologies through C–C bond cleavage and Dioxygen activation.
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Direct Tryptophols Synthesis from 2‑Vinylanilines and Alkynes via CC Triple Bond Cleavage and Dioxygen Activation
2016Co-Authors: Tao Shen, Yiqun Zhang, Yufeng Liang, Ning JiaoAbstract:An unexpected metal-free CC triple bond cleavage, Dioxygen activation, and reassembly into tryptophol derivatives has been developed. This chemistry provides a novel, simple, and efficient approach to highly valuable tryptophol derivatives from simple substrates under mild conditions. The mechanistic studies may promote the discovery of new methodologies through C–C bond cleavage and Dioxygen activation
Wonwoo Nam - One of the best experts on this subject based on the ideXlab platform.
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autocatalytic Dioxygen activation to produce an iron v oxo complex without any reductants
Chemical Communications, 2017Co-Authors: Muniyandi Sankaralingam, Wonwoo Nam, Yongmin Lee, Anil Kumar Vardhaman, Shunichi FukuzumiAbstract:An iron(V)-oxo complex with a tetraamido macrocyclic ligand, [(TAML)FeV(O)]−, was produced by reacting [(TAML)FeIII]− with Dioxygen without any electron source in acetone at 298 K. The autocatalytic mechanism of Dioxygen activation for the formation of an iron(V)-oxo complex has been clarified based on the autocatalysis by radical chain initiators.
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status of reactive non heme metal oxygen intermediates in chemical and enzymatic reactions
Journal of the American Chemical Society, 2014Co-Authors: Kallol Ray, Florian Felix Pfaff, Bin Wang, Wonwoo NamAbstract:Selective functionalization of unactivated C–H bonds, water oxidation, and Dioxygen reduction are extremely important reactions in the context of finding energy carriers and conversion processes that are alternatives to the current fossil-based oil for energy. A range of metalloenzymes achieve these challenging tasks in biology by using cheap and abundant transition metals, such as iron, copper, and manganese. High-valent metal–oxo and metal–Dioxygen (superoxo, peroxo, and hydroperoxo) cores act as active intermediates in many of these processes. The generation of well-described model compounds can provide vital insights into the mechanisms of such enzymatic reactions. This perspective provides a focused rather than comprehensive review of the recent advances in the chemistry of biomimetic high-valent metal–oxo and metal–Dioxygen complexes, which can be related to our understanding of the biological systems.
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Mononuclear Metal-O-2 Complexes Bearing Macrocyclic N-Tetramethylated Cyclam Ligands
'American Chemical Society (ACS)', 2012Co-Authors: Cho Jaeheung, Sarangi Ritimukta, Wonwoo NamAbstract:Metalloenzymes activate Dioxygen to carry out a variety of biological reactions, including the biotransformation of naturally occurring molecules, oxidative metabolism of xenobiotics, and oxidative phosphorylation. The Dioxygen activation at the catalytic sites of the enzymes occurs through several steps, such as the binding of O2 at a reduced metal center, the generation of metal???superoxo and ???peroxo species, and the O???O bond cleavage of metal???hydroperoxo complexes to form high-valent metal-oxo oxidants. Because these mononuclear metal???Dioxygen (M???O2) adducts are implicated as key intermediates in Dioxygen activation reactions catalyzed by metalloenzymes, studies of the structural and spectroscopic properties and reactivities of synthetic biomimetic analogues of these species have aided our understanding of their biological chemistry. One particularly versatile class of biomimetic coordination complexes for studying Dioxygen activation by metal complexes is M???O2 complexes bearing the macrocyclic N-tetramethylated cyclam (TMC) ligand. This Account describes the synthesis, structural and spectroscopic characterization, and reactivity studies of M???O2 complexes bearing tetraazamacrocyclic n-TMC ligands, where M ??? Cr, Mn, Fe, Co, and Ni and n = 12, 13, and 14, based on recent results from our laboratory. We have used various spectroscopic techniques, including resonance Raman and X-ray absorption spectroscopy, and density functional theory (DFT) calculations to characterize several novel metal???O2 complexes. Notably, X-ray crystal structures had shown that these complexes are end-on metal-superoxo and side-on metal-peroxo species. The metal ions and the ring size of the macrocyclic TMC ligands control the geometric and electronic structures of the metal???O2 complexes, resulting in the end-on metal???superoxo versus side-on metal???peroxo structures. Reactivity studies performed with the isolated metal-superoxo complexes reveal that they can conduct electrophilic reactions such as oxygen atom transfer and C???H bond activation of organic substrates. The metal???peroxo complexes are active oxidants in nucleophilic reactions, such as aldehyde deformylation. We also demonstrate a complete intermolecular O2-transfer from metal(III)???peroxo complexes to a Mn(II) complex. The results presented in this Account show the significance of metal ions and supporting ligands in tuning the geometric and electronic structures and reactivities of the metal???O2 intermediates that are relevant in biology and in biomimetic reactions
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geometric and electronic structure and reactivity of a mononuclear side on nickel iii peroxo complex
Nature Chemistry, 2009Co-Authors: Jaeheung Cho, Ritimukta Sarangi, Jamespandi Annaraj, Sung Yeon Kim, Minoru Kubo, Takashi Ogura, Edward I Solomon, Wonwoo NamAbstract:Metal-Dioxygen adducts, such as metal-superoxo and -peroxo species, are key intermediates often detected in the catalytic cycles of Dioxygen activation by metalloenzymes and biomimetic compounds. The synthesis and spectroscopic characterization of an end-on nickel(II)-superoxo complex with a 14-membered macrocyclic ligand was reported previously. Here we report the isolation, spectroscopic characterization, and high-resolution crystal structure of a mononuclear side-on nickel(III)-peroxo complex with a 12-membered macrocyclic ligand, [Ni(12-TMC)(O(2))](+) (1) (12-TMC = 1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclododecane). Different from the end-on Ni(II)-superoxo complex, the Ni(III)-peroxo complex is not reactive in electrophilic reactions, but is capable of conducting nucleophilic reactions. The Ni(III)-peroxo complex transfers the bound Dioxygen to manganese(II) complexes, thus affording the corresponding nickel(II) and manganese(III)-peroxo complexes. The present results demonstrate the significance of supporting ligands in tuning the geometric and electronic structures and reactivities of metal-O(2) intermediates that have been shown to have biological as well as synthetic usefulness in biomimetic reactions.
