Manganese Redox Enzymes and Model Systems: Properties, Structures, and Reactivity

Law, Neil A.; Caudle, M. Tyler; Pecoraro, Vincent L.

doi:10.1016/s0898-8838(08)60152-x

Cited by 199 publications

(134 citation statements)

References 365 publications

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“…Other di-Mn and diiron enzymes similarly shuttle between di-Fe(II) and di-Fe(III) or di-Mn(II) and di-Mn(III). These proteins include manganese catalase (21,22) and rubrerythrin, which is believed to be an NADH-dependent peroxide reductase (23).…”

Section: Discussionmentioning

confidence: 99%

De novo design of catalytic proteins

Kaplan

DeGrado

2004

Proc. Natl. Acad. Sci. U.S.A.

308

290

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The de novo design of catalytic proteins provides a stringent test of our understanding of enzyme function, while simultaneously laying the groundwork for the design of novel catalysts. Here we describe the design of an O2-dependent phenol oxidase whose structure, sequence, and activity are designed from first principles. The protein catalyzes the two-electron oxidation of 4-aminophenol (kcat͞KM ‫؍‬ 1,500 M ؊1 ⅐min ؊1 ) to the corresponding quinone monoimine by using a diiron cofactor. The catalytic efficiency is sensitive to changes of the size of a methyl group in the protein, illustrating the specificity of the design.T he de novo design of proteins provides a stringent test of our understanding of their molecular mechanisms of action (1-3). Recently, it has become possible to design proteins with novel three-dimensional structures (4), which has laid the groundwork for the elaboration of function. Catalysis provides a particularly challenging function to achieve, because a successfully designed protein catalyst must bind and precisely orient substrates, transition states, and intermediates adjacent to catalytic groups such as metal ions, general acids, and͞or general bases. Two approaches to the design of catalytic proteins include automated sequence design, in which a novel catalytic site is engineered into a natural protein by mutating a subset of its side chains (5-7), and de novo protein design, which requires the simultaneous design of the entire backbone structure and sequence (2). The first method has the advantage of separating the problem of protein design and folding from the more restricted problem of designing an active site. The second approach has the potential advantage of greater applicability in terms of the sizes and shapes of substrates that can be accommodated. Furthermore, de novo protein design critically tests our understanding of how an amino acid sequence dictates both the folding as well as the activity of a protein.To date, most work on the design of catalytic proteins has focused on hydrolysis of activated 4-nitrophenyl esters, using an active site histidine side chain as a nucleophilic catalyst. Automated sequence design methods have been used to design a variant of thioredoxin that hydrolyses 4-ntirophenyl acetate with a rate enhancement of Ϸ25-fold (7), when the value of k cat ͞K M was compared to the second order rate constant for hydrolysis of 4-methyl imidazole. Proteins with similar or greater catalytic efficiencies were observed frequently in a library of four-helix bundle proteins, whose polar exterior residues were randomly selected from Lys, His, Glu, Gln, Asp, and Asn (8). Baltzer and Nilsson (1) have designed a series of helical bundles that employ His residues to promote hydrolysis and intrapeptide acyl transfer reactions. It has also been possible to design helical bundles that catalyze decarboxylation of oxaloacetate (9), in one case by recognizing a key aldamine intermediate in the reaction (10).Automated sequence design has also been used to design catalytic meta...

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Section: Discussionmentioning

confidence: 99%

De novo design of catalytic proteins

Kaplan

DeGrado

2004

Proc. Natl. Acad. Sci. U.S.A.

308

290

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“…Many of the biosystems described above have been modeled by inorganic chemists and EPR spectroscopy serves as an essential tool in the evaluation of the electronic and geometric properties of these synthetic analogues [1,[88][89][90]. In particular, Mn(II):nucleotide adducts and other metal-bound small-molecule constructs (e.g., Mn(II) bound to synthetic RNA) have attracted much attention owing to the involvement of these species in crucial biochemical processes such as ATP hydrolysis [31], R.NA sequence modification [33,91], and cellular signaling.…”

Section: Past Studiesmentioning

confidence: 99%

“…A noteworthy alternative to the typical field-modulated CW EPR experiment, which also gives absorptive EPR line shapes, is the method of rapid adiabatic passage ( (inhibitors) were bound to the Mn(II) active site of Fosa were correlated to changes in both coordination number as well as the nature of the ligand field. Importantly, this data helped point to a possible molecular mechanism by which FosA helps bacteria subvert the effects of the broad-spectrum antibiotic fosfomycin.Many of the biosystems described above have been modeled by inorganic chemists and EPR spectroscopy serves as an essential tool in the evaluation of the electronic and geometric properties of these synthetic analogues [1,[88][89][90]. In particular, Mn(II):nucleotide adducts and other metal-bound small-molecule constructs (e.g., Mn(II) bound to synthetic RNA) have attracted much attention owing to the involvement of these species in crucial biochemical processes such as ATP hydrolysis [31], R.NA sequence modification [33,91], and cellular signaling.…”

mentioning

confidence: 99%

Multifrequency pulsed EPR studies of biologically relevant manganese(II) complexes

et al. 2007

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Electron paramagnetic resonance studies at multiple frequencies (MF EPR) can provide detailed electronic structure descriptions of unpaired electrons in organic radicals, inorganic complexes, and metalloenzymes. Analysis of these properties aids in the assignment of the chemical environment surrounding the paramagnet and provides mechanistic insight into the chemical reactions in which these systems take part. Herein, we present results from pulsed EPR studies performed at three different frequencies (9, 31, and 130 GHz) on [Mn(II)(H 2 O) 6 ] 2+ , Mn(II) adducts with the nucleotides ATP and GMP, and the Mn(II)-bound form of the hammerhead ribozyme (MnHH). Through line shape analysis and interpretation of the zero-field splitting values derived from successful simulations of the corresponding continuous-wave and field-swept echodetected spectra, these data are used to exemplify the ability of the MF EPR approach in distinguishing the nature of the first ligand sphere. A survey of recent results from pulsed EPR, as well as pulsed electron-nuclear double resonance and electron spin echo envelope modulation spectroscopic studies applied to Mn(II)-dependent systems, is also presented. Mn-Containing Biological SystemsManganese operates as a cofactor in numerous proteins, serving both catalytic and structural roles [1][2][3][4]. Many Mn-dependent enzymes take advantage o f the rich redox chemistry available to the metal, accessing the +2, +3, +4, and perhaps even the +5 oxidation states during their turnover. For example, Mn-superoxide dismutase (MnSOD), which detoxifies the cell of the superoxide radical , cycles between the Mn(II) and Mn(III) oxidation states via the ping-pong type mechanism shown below [5][6][7][8][9].(1a) (1b) Other examples of such mononuclear redox-active enzymes include the manganese peroxidase responsible for lignin degradation by white-rot fungus [10][11][12]; a unique Mndependent form of lipoxygenase [13][14][15][16]; oxalate decarboxylase [17,18]; as well as an extradiol catechol dioxygenase [19][20][21]. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptIn order to help minimize kinetic and thermodynamic penalties associated with electron transfer events and the execution of chemical reactions, two or more metal centers can be coupled together to provide active sites capable of conducting multiple electrons while still operating within a physiologically accessible range of reduction potentials [22]. Only three such examples of redox-active polynuclear Mn enzymes are known: Mn-catalase that disproportionates hydrogen peroxide [23][24][25][26]; a Mn form of ribonucleotide reductase (Mn-RNR) [27,28]; and, arguably the most recognized Mn-dependent enzyme, the photosynthetic core of green plants, algae, and certain cyanobacteria termed photosystem II (PSII) [29,30]. Through a series of photoinitiated electron transfer events, oxidizing equivalents are stored on the tetranuclear Mn core of PSII -the oxygen-evolving complex (OEC) -which then extracts four electr...

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“…[1][2][3][4] Mononuclear manganese centres have been found in the oxygen evolving center (OEC) of photosystem II (PS-II) 5 and in numerous enzymes, 6 including the superoxide dismutase, Mn-SOD, 7 and Mn-dioxygenase. 8 Dinuclear manganese centres, on the other hand, have been found in various metalloenzymes, 14 including catalase, 9-11 Mn-ribonucleotide reductase 12 and arginase.…”

Section: Introductionmentioning

confidence: 99%

Designer ligands. part 15. synthesis and characterisation of novel Mn(lI), Ni(II) and Zn(II) complexes of 1,10-phenanthroline-derived ligands.

Wellington¹,

Kaye²,

Watkins³

2010

Arkivoc

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Series of manganese(II), nickel(II) and zinc(II) complexes have been prepared using 1,10-phenanthroline-derived ligands, and their coordination geometries have been assigned using infrared data. It is apparent that, depending on the ligand, the metal centres adopt octahedral, tetrahedral and distorted tetrahedral coordination geometries. The catecholase activity of the manganese(II) complexes has also been investigated.

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Manganese Redox Enzymes and Model Systems: Properties, Structures, and Reactivity

Cited by 199 publications

References 365 publications

De novo design of catalytic proteins

De novo design of catalytic proteins

Multifrequency pulsed EPR studies of biologically relevant manganese(II) complexes

Designer ligands. part 15. synthesis and characterisation of novel Mn(lI), Ni(II) and Zn(II) complexes of 1,10-phenanthroline-derived ligands.

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