Download or read book Spectroscopic Characterization of Binuclear Non heme Iron and MN FE Active Sites written by Yeonju Kwak and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Binuclear non-heme iron enzymes catalyze various reactions including H-atom abstraction, desaturation, hydroxylation, and electrophilic aromatic substitution through O2 activation. In addition, they protect cells from oxidative stress and regulate iron levels in the cell. These enzymes utilize two irons and have common structural motif of 2-His / 4-carboxylate. Despite the enzymes' structural similarities, subtle changes at their active sites allow these enzymes to have different reactivities. Understanding the active site structures of these enzymes and the key mechanistic features related to these structures can provide a basis for potential applications: they could be drug inhibition targets to treat cancer, diabetes, and pathogenic diseases; they could work as biocatalysts; and they could carry out bioremediation reactions. In this dissertation, studies that examine three binuclear non-heme iron and Mn/Fe enzyme active sites (class Ic ribonucleotide reductase, ferritin variants, and bacterioferritin) and peroxo-bridged biferric model complexes are described. A combined spectroscopic methodology of nuclear resonance vibrational spectroscopy (NRVS), circular dichroism (CD), magnetic circular dichroism (MCD), and variable temperature, variable field (VTVH) MCD is used to probe geometric and electronic structures of Mn and Fe centers in protein active site and in model complexes.

Download or read book Spectroscopic and Theroretical Definition of Binuclear Non heme Iron Active Sites written by Yi-Shan Yang and published by . This book was released on 1999 with total page 558 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Spectroscopic and Theoretical Elucidation of Structural Contributions to Reactivity in Binuclear Non heme Iron Enzymes written by Jennifer Kathleen Schwartz and published by . This book was released on 2008 with total page 568 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Spectroscopic Studies of Mixed valent Binuclear Non heme Iron Active Sites written by James Malcolm McCormick and published by . This book was released on 1991 with total page 536 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Bioinorganic Spectroscopy Structure function Correlations in Binuclear Non heme Iron Enzymes and Developing Nuclear Resonance Vibrational Spectroscopy for Characterization of Enzyme Intermediates written by Caleb Branson Bell and published by . This book was released on 2010 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The foci of this dissertation are: 1) combined use of spectroscopies for mechanistic understanding of the oxygen reactions of various non-heme iron enzymes and related model complexes, and 2) the development of the recently described nuclear vibrational resonance spectroscopy (NRVS) coupled with density functional calculations (DFT) for characterization of non-heme iron enzyme intermediates. Binuclear non-heme iron enzymes are involved in many medically and industrially important processes such as DNA synthesis by ribonucleotide reductase (RNR), conversion of methane to methanol by methane monooxygenase (MMO), fatty acid desaturation by [Delta]9 desaturase, iron storage and homeostasis by ferritins, degradation of aromatic compounds by various bacterial monooxygenases (ToMO, T4MO, etc.) and antibiotic biogenesis by p-aminobenzoate N-oxygenase (AurF), etc. Interestingly, these diverse reactions typically begin with O2 reacting with a biferrous active site, coordinated by highly conserved protein ligands (ExxH motifs) in four [Alpha]-helix bundles. Moreover, spectroscopically and chemically similar intermediates can be detected in many of the enzyme systems. The best studied in this family are RNRs, where biferric peroxo intermediates (P and P'), and the high-valent Fe(III)Fe(IV) intermediate X have been stabilized and spectroscopically characterized in wt and numerous variants. De novo designed four [Alpha]-helix bundles have been synthesized (the ~140 amino acid dui ferri (DF) peptide family) and are good models for binuclear non-heme iron enzymes. These systems provide a protein environment and can be viewed as a bridge between inorganic model complexes and native proteins. The pseudo-symmetric single chain version (DFsc) coordinates two ferrous ions by two His and four Glu amino acid residues. Circular dichroism (CD), magnetic CD (MCD) and variable-temperature variable-field MCD (VTVH MCD) show that this "active site" in DFsc has a 4-coordinate and 5-coordinate (4C+5C) geometry that is weakly antiferromagnetically coupled (J [approximately equal to] --2 cm-1) indicative of [Mu]1,3 carboxylate bridges, highly similar to RNR biferrous structures. Extended x-ray absorption fine structure (EXAFS) data are consistent with this assignment and show that one terminal carboxylate residue coordinates in a bidentate fashion. Changes in the CD/MCD/VTVH MCD and EXAFS spectra in the Y51L and E11D variants show that the 4C site is proximal to (but not bound by) Y51 and the bidentate carboxylate is coordinated to the 5C iron. Open coordination positions on both irons allow for dioxygen to react rapidly with the biferrous site. The reaction of biferrous DFsc with dioxygen yields a 520 nm ([Epsilon] = [weak approximation to]1200 M-1cm-1) species with a formation rate of 2 s-1, again similar to RNR (the Class Ia RNR from Escherichia coli has a dioxygen reaction rate of ~1 s-1, however the first species formed (intermediate P) has [Lambda]max = 700 nm). The resonance Raman (rR) spectrum obtained by excitation into the 520 nm feature in DFsc (and the E11D variant) proves this chromophore arises from a Tyr to ferric charge transfer (CT) transition. The 520 nm feature is lost by substitution of Y51 but not Y18, thus Y51 binds to the site after reaction with dioxygen. Subsequent binding of Y51 functions as an internal spectral probe of the dioxygen reaction and as a proton source that would promote loss of hydrogen peroxide. Coordination by a ligand that functions as a proton source could be a structural mechanism used by natural binuclear iron enzymes to drive their reactions past peroxo biferric level intermediates. RNR's can be divided into 3 major classes based on the radical generating machinery. Class I RNR's utilize a dimetal cofactor that reacts with dioxygen and can be subdivided into Classes Ia, Ib and Ic based on sequence homology and metal dependency. Class Ia enzymes are the best studied an present in higher organisms including human (host) while Class Ib enzymes are typically found in pathogens. CD, MCD and VTVH MCD data on biferrous loaded Class Ib RNR from Bacillus cereus allow assignment of the active site as 4C+5C in solution, resolving discrepancies from available crystal structures. Differences in the zero-field splitting parameters (D and E) and magnetic coupling extracted from fits to the VTVH MCD data can be ascribed to differences in the bridging carboxylate conformations. FeII loading, monitored by CD, shows cooperative binding with Kd 100 mM, significantly stronger that the metal binding in Class Ia. This provides the pathogen a competitive advantage relative to host in physiological, iron-limited environments Returning to Class Ia, the recently discovered intermediate P' notably lacks structural definition. This is mainly due to the lack of spectroscopic handles from which to obtain the needed experimental data. What is know, however, is that this species directly forms intermediate X and is directly derived from the well-defined intermediate P. Spectroscopically, P' has Mössbauer isomer shifts ([lowercase Delta] = 0.52 and 0.45 mm/s) that are significantly lower than the cis-[Mu]1,2 peroxo P ([lowercase Delta] = 0.63 mm/s) and lacks the ~700 nm peroxo to ferric CT suggesting some change in coordination mode or protonation may be involved in P -- P'. Comparisons of the reduced and oxidized crystal structures show differences in carboxylate coordination modes and water binding that must occur at some stage along the reaction coordinate. All of these potential structural perturbations were systematically incorporated into computational models of the intermediate site and correlated with experimental data using density functional theory (DFT). Two potential reaction pathways consistent with available experimental data were found. The first involves water addition to Fe1 of the cis-[Mu]-1,2 peroxo intermediate P causing opening of a bridging carboxylate to form intermediate P' which has an increased electron affinity and is activated for proton-coupled electron transfer to form the Fe(III)Fe(IV) intermediate X. While the second, more energetically favorable pathway, involves addition of a proton to a terminal carboxylate ligand in the site which increases the electron affinity and triggers electron transfer to form X. Vibrational characterization could, in principle, distinguish these pathways. However, the lack of a reasonably intense chromophore precludes rR experiments. The recently available method of nuclear vibrational resonance spectroscopy (NRVS) does not have these chromophoric constraints and can provide the needed vibrational data for P'--and many other "spectroscopically challenged" intermediates in non-heme iron biochemistry. The vibrations enhanced in NRVS are typically lower in energy and differ from those observed in rR, thus studies on well defined model complexes are needed prior to intermediate studies. A series of mononuclear Fe(IV)=O have been characterized by NRVS coupled with DFT calculations to define NRVS spectral assignments and set a foundation for vibrational characterization of non-heme iron enzyme intermediates. These studies show that the NRVS spectrum is rich in structural information. Of the four Fe(IV)=O models, supported by the 1, 4, 8, 11-tetramethyl-1,4,8,11-tetraazacyclotetradecane (TMC); N, N-bis(2-pyridylmethyl)-N-bis(2-pyridyl) methylamine (N4Py); N-benzyl-N, N', N'-tris(2-pyridylmethyl)-1,2-diaminoethane (BnTPEN); and 1,1,1-tris{2-[N(2)-(1,1,3,3-tetramethylguanidino)]ethyl}amine (TMG3tren) ligand sets, only the trigional bipyramidal geometry (relative to the 6C approximatly C4v geometry of TMC, N4Py and BnTPEN) enforced by the TMG3tren ligand affords a high-spin species. Isotope sensitive Fe-O stretches are observed for all complexes at 820 to 831 cm-1. However, at lower energy (

Download or read book Spectroscopic and Structural Studeis sic of Core Variation in Binuclear Iron Families written by Pin-Pin Wei and published by . This book was released on 2006 with total page 176 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Spectroscopic and Reactivity Studies of Binuclear Non heme Iron Complexes written by Subhasish Mukerjee and published by . This book was released on 1996 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Spectroscopic and Reactivity Studies of Mononuclear and Binuclear Non heme Iron Complexes written by Bala Sundari T. Kasibhatla and published by . This book was released on 1998 with total page 478 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Spectroscopic and Computational Studies of Mononuclear Nonheme Iron Enzymes written by Kenneth M. Light and published by . This book was released on 2014 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Mononuclear nonheme iron enzymes (NH Fe enzymes) catalyze a variety of biological reactions. A large group of NH Fe enzymes use a ferrous active site to activate dioxygen towards reaction with substrate, and require an additional cofactor as a source of electrons necessary for catalysis. The main part of this thesis involves the application of a circular dichroism (CD), magnetic circular dichroism (MCD) and variable temperature, variable-field MCD (VTVH MCD) spectroscopic methodology to a series of alpha-ketoglurate-dependent (alpha-KG-dependent) enzymes for the purpose of understanding how this enzyme family and the NH Ferrous enzymes in general induce the dissociation the generation of a 5C site for dioxgyen reactivity, as well as how dioxygen binding is oriented for proper catalysis. In addition to catalyzing oxidation of organic substrates, NH Fe enzymes are also involved in the catalytic hydrolysis and hydration of substrates. A prominent example of this is nitrile hydratases (NHases), unusual low-spin (LS) Ferric or Cobaltic enzymes that catalyze the conversion of nitriles to amides in soil bacteria. Another part of this thesis involves the spectroscopic characterization of a ferric NHase for the determination of its active site geometric and electronic structure, which are used to calibrate a computational model which is extended to explore the NHase catalytic mechanism.

Download or read book Ribonucleotide Reductase written by Kristoffer Andersson and published by Nova Publishers. This book was released on 2008 with total page 236 pages. Available in PDF, EPUB and Kindle. Book excerpt: The subject of this book is the amazing enzyme ribonucleotide reductase (RNR), the enzyme responsible for the conversion of ribonucleotides to deoxyribonucleotides. The prerequisite for DNA-synthesis and DNA-repair in all living cells is the supply of the four deoxyribonucleotides. Such molecules result from the enzymatically difficult radical-induced reduction of ribonucleotides, a multistep chemical process catalyzed by RNR. RNR was the first enzyme in which the presence of an amino acid radical (a tyrosyl) in E. coli Class Ia RNR has been proven; since then several other biological amino acid radical species have been found on e.g. tryptophan, glycine, cysteine, lysine residues and on amino acid derived small cofactors like 2 tryptophanes in thryptophan-trypthanyl-radical or cysteine-tyrosyl-radical in other enzymes. As all known cellular life forms store their genetic information as DNA, RNR is likely to be found in all growing cells of every living organism, a fact that is confirmed by a rapidly increasing number of genomic screenings.

Download or read book Index Medicus written by and published by . This book was released on 2004 with total page 2520 pages. Available in PDF, EPUB and Kindle. Book excerpt: Vols. for 1963- include as pt. 2 of the Jan. issue: Medical subject headings.

Download or read book Chlorophylls and Bacteriochlorophylls written by Bernhard Grimm and published by Springer Science & Business Media. This book was released on 2007-03-14 with total page 603 pages. Available in PDF, EPUB and Kindle. Book excerpt: The first dedicated new work since 1991, this book reviews recent progress and current studies in the chemistry, metabolism and spectroscopy of chlorophylls, bacteriochlorophylls and their protein complexes. Also discussed is progress on the applications of chlorophylls as photosensitizers in photodynamic therapy of cancerous tumours, and as molecular probes in biochemistry, medicine, plant physiology, ecology and geochemistry. Each section offers an introductory overview followed by concise, focused and fully-referenced chapters written by experts.

Download or read book Dioxygen Activation and Homogeneous Catalytic Oxidation written by L. I. Simándi and published by Elsevier Publishing Company. This book was released on 1991 with total page 748 pages. Available in PDF, EPUB and Kindle. Book excerpt: Dioxygen activation is a rapidly developing field in which research is directed at (1) modelling of biological oxidations, (2) design and utilization of new catalysts for oxidative transformations of organic substrates, (3) application of O 2 (and H 2 O 2 ) as a cheap oxidant in the manufacture of fine and bulk chemicals. Provided here is a collection of both review and original papers covering all aspects of dioxygen activation. All papers provide background information of previous work. Reactions mechanisms are extensively treated and a keyword index facilitates quick orientation. The book should prove invaluable to organic, bioinorganic and coordination chemists as well as biochemists interested in homogeneous catalysis.

Download or read book Annual Review written by Bunshi Kagaku Kenkyūjo and published by . This book was released on 2000 with total page 618 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Electronic Spectroscopy of Transition Metal Dimers Relevant to Biological Electron Transfer and Catalysis written by Daniel R. Gamelin and published by . This book was released on 1997 with total page 228 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Directory of Graduate Research written by American Chemical Society. Committee on Professional Training and published by . This book was released on 2005 with total page 1932 pages. Available in PDF, EPUB and Kindle. Book excerpt: Faculties, publications and doctoral theses in departments or divisions of chemistry, chemical engineering, biochemistry and pharmaceutical and/or medicinal chemistry at universities in the United States and Canada.

Download or read book 2 Oxoglutarate Dependent Oxygenases written by Christopher J Schofield and published by Royal Society of Chemistry. This book was released on 2015-05-06 with total page 508 pages. Available in PDF, EPUB and Kindle. Book excerpt: Since the discovery of the first examples of 2-oxoglutarate-dependent oxygenase-catalysed reactions in the 1960s, a remarkably broad diversity of alternate reactions and substrates has been revealed, and extensive advances have been achieved in our understanding of the structures and catalytic mechanisms. These enzymes are important agrochemical targets and are being pursued as therapeutic targets for a wide range of diseases including cancer and anemia. This book provides a central source of information that summarizes the key features of the essential group of 2-oxoglutarate-dependent dioxygenases and related enzymes. Given the numerous recent advances and biomedical interest in the field, this book aims to unite the latest research for those already working in the field as well as to provide an introduction for those newly approaching the topic, and for those interested in translating the basic science into medicinal and agricultural benefits. The book begins with four broad chapters that highlight critical aspects, including an overview of possible catalytic reactions, structures and mechanisms. The following seventeen chapters focus on carefully selected topics, each written by leading experts in the area. Readers will find explanations of rapidly evolving research, from the chemistry of isopenicillin N synthase to the oxidation mechanism of 5-methylcytosine in DNA by ten-eleven-translocase oxygenases.