| 1. |
- Chen, Shilu, et al.
(författare)
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Reaction mechanism of the binuclear zinc enzyme glyoxalase II : A theoretical study
- 2009
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Ingår i: Journal of Inorganic Biochemistry. - : Elsevier BV. - 0162-0134 .- 1873-3344. ; 103:2, s. 274-281
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Tidskriftsartikel (refereegranskat)abstract
- The glyoxalase system catalyzes the conversion of toxic methylglyoxal to nontoxic d-lactic acid using glutathione (GSH) as a coenzyme. Glyoxalase II (GlxII) is a binuclear Zn enzyme that catalyzes the second step of this conversion, namely the hydrolysis of S-d-lactoylglutathione, which is the product of the Glyoxalase I (GlxI) reaction. In this paper we use density functional theory method to investigate the reaction mechanism of GlxII. A model of the active site is constructed on the basis of the X-ray crystal structure of the native enzyme. Stationary points along the reaction pathway are optimized and the potential energy surface for the reaction is calculated. The calculations give strong support to the previously proposed mechanism. It is found that the bridging hydroxide is capable of performing nucleophilic attack at the substrate carbonyl to form a tetrahedral intermediate. This step is followed by a proton transfer from the bridging oxygen to Asp58 and finally C–S bond cleavage. The roles of the two zinc ions in the reaction mechanism are analyzed. Zn2 is found to stabilize the charge of tetrahedral intermediate thereby lowering the barrier for the nucleophilic attack, while Zn1 stabilizes the charge of the thiolate product, thereby facilitating the C–S bond cleavage. Finally, the energies involved in the product release and active-site regeneration are estimated and a new possible mechanism is suggested.
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| 2. |
- Dimitrakopoulou, Anastasia, et al.
(författare)
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Synthesis, structure and interactions with DNA of novel tetranuclear, [Mn-4(II/II/II/IV)] mixed valence complexes
- 2008
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Ingår i: Journal of Inorganic Biochemistry. - : Elsevier BV. - 1873-3344 .- 0162-0134. ; 102:4, s. 618-628
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Tidskriftsartikel (refereegranskat)abstract
- Reaction of Mn(II) with phenoxyalkanoic acids and di-2-pyridyl ketone oxime (Hpko) leads to neutral tetranuclear complexes of the general formula Mn-4(O)(pko)(4)(phenoxyalkanoato)(4) (phenoxyalkanoic acids: H-mcpa = 2-methyl-4-chloro-phenoxy-acetic acid, H-2,4,5-T = 2,4.5-trichloro-phenoxy-acetic acid or H3,4-D = 3,4-dichloro-phenoxy-acetic acid). The compounds were synthesized by adding di2-pyridyl ketone oxime to MnCl2 in the presence of the sodium salts of the alkanoic acids in methanol. The crystal structure of Mn-4(II/II/ II/IV)(O)(pko)4(()2,4,5-T)(4) . 2.5CH(3)OH . 0.25H(2)O 1 shows that the complex consists of a [Mn-4( mu(4)-O)](8+) core with a Mn(IV) and 3 Mn(II) ions in octahedral environment and a mu(4)-O atom bridging the four manganese ions. Spectroscopic studies of the interaction of these tetranuclear clusters with DNA showed that these compounds bind to dsDNA. The binding strength of the Mn-4(II/II/II/ IV)(O)(pko)(4)(2,4,5-T)(4) complex for calf thymus DNA is equal to 1.1 X 10(4) M-1. Among the deoxyribonucleotides they bind preferentially to deoxyguanylic acid (dGMP). Competitive studies with ethidium bromide (EthBr) showed that the Mn-4(II/II/II/ IV)(O)(pko)(4)(2,4,.5-T)(4) complex exhibited the ability to displace the DNA-bound EthBr indicating that the complex binds to DNA via intercalation in strong competition with EthBr for the intercalative binding site. Additionally, DNA electrophoretic mobility experiments showed that all three complexes, at low cluster concentration, are obviously capable of binding to pDNA causing its cleavage (relaxation) at physiological pH and temperature. At higher cluster concentration, catenated dimer forms of pDNA was formed.
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| 3. |
- Dong, Weibing, et al.
(författare)
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Preparation, structures and electrochemical property of phosphine substituted diiron azadithiolates relevant to the active site of Fe-only hydrogenases
- 2007
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Ingår i: Journal of Inorganic Biochemistry. - : Elsevier BV. - 0162-0134 .- 1873-3344. ; 101:3, s. 506-513
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Tidskriftsartikel (refereegranskat)abstract
- Mono- and di-phosphine diiron azadithiolate complexes [{(mu-SCH2)(2)N(4-NO2C6H4)}Fe-2(CO)(5)(PMe3)] (2), [{(mu-SCH2)(2)N(4NO(2)C(6)H(4))} {Fe(CO)(2)L}(2)] (3, L = PMe3; 4, PMe2Ph) and the mu-hydride diiron complex [3(FeHFe)](+)[PF6](-) were prepared as biontimetic models of the active site of Fe-only hydrogenases. The complexes 2-4 and [3(FeHFe)](+)[PF6](-) were characterized by IR P-31, H-1 and C-13 NMR spectra and their molecular structures were determined by single crystal X-ray analyses. The PMe3 ligand in complex 2 lies on the basal position. The PMe3-disubstituted complex 3 exists as two configuration isomers, transoid basal/basal and apical/basal, in the crystalline state, while two PMe2Ph ligands of 4 are in an apical/basal orientation. The variable temperature P-31 NMR spectra of 2 and 3 were made to have an insight into the existence of the possible conformation isomers of 2 and 3 in solution. The [3(FeHFe)](+) cation possesses the sole transoid ba/ba geometry as other reported mu-hydride diiron analogues. The electrocatalytic property of {(mu-SCH2)(2)NC6H5}[Fe(CO)(2)PMe3](2) (5) was studied for proton reduction in the presence of HOAc.
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| 4. |
- Flock, Ulrika, et al.
(författare)
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Exploring the terminal region of the proton pathway in the bacterial nitric oxide reductase
- 2009
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Ingår i: Journal of Inorganic Biochemistry. - : Elsevier BV. - 0162-0134 .- 1873-3344. ; 103:5, s. 845-850
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Tidskriftsartikel (refereegranskat)abstract
- The c-type nitric oxide reductase (cNOR) from Paracoccus (P.) denitrificans is an integral membrane protein that catalyzes NO reduction; 2NO+2e(-)+2H(+)-->N(2)O+H(2)O. It is also capable of catalyzing the reduction of oxygen to water, albeit more slowly than NO reduction. cNORs are divergent members of the heme-copper oxidase superfamily (HCuOs) which reduce NO, do not pump protons, and the reaction they catalyse is non-electrogenic. All known cNORs have been shown to have five conserved glutamates (E) in the catalytic subunit, by P. denitrificans numbering, the E122, E125, E198, E202 and E267. The E122 and E125 are presumed to face the periplasm and the E198, E202 and E267 are located in the interior of the membrane, close to the catalytic site. We recently showed that the E122 and E125 define the entry point of the proton pathway leading from the periplasm into the active site [U. Flock, F.H. Thorndycroft, A.D. Matorin, D.J. Richardson, N.J. Watmough, P. Adelroth, J. Biol. Chem. 283 (2008) 3839-3845]. Here we present results from the reaction between fully reduced NOR and oxygen on the alanine variants of the E198, E202 and E267. The initial binding of O(2) to the active site was unaffected by these mutations. In contrast, proton uptake to the bound O(2) was significantly inhibited in both the E198A and E267A variants, whilst the E202A NOR behaved essentially as wildtype. We propose that the E198 and E267 are involved in terminating the proton pathway in the region close to the active site in NOR.
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| 5. |
- Gorzsás, András, et al.
(författare)
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Speciation in Aqueous Vanadate – Ligand and Peroxovanadate – Ligand systems
- 2009
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Ingår i: Journal of Inorganic Biochemistry. - : Elsevier BV. - 0162-0134 .- 1873-3344. ; 103:4, s. 517-526
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Tidskriftsartikel (refereegranskat)abstract
- In the present focused review, the speciation studies of aqueous vanadate-ligand (L) and peroxovanadate-L systems are addressed. The paper focuses solely on the systems studied at our department in the context of potential insulin-enhancing effects, including the following ligands: imidazole, alanylhistidine, alanylserine, lactate, picolinate, citrate, phosphate, maltol, and uridine. We summarise the results of detailed and thorough potentiometric (glass electrode) and 51V NMR (Bruker AMX-500 MHz) spectroscopic studies, performed at 25 °C in 0.150 M Na(Cl), a medium representing human blood. The importance of experimental conditions is discussed and illustrated. A detailed overview of our methodology, based on combining potentiometric and 51V integral and chemical shift data by means of the computer program LAKE, is also given. We list the important steps of equilibrium analysis and the kinds of information available from different sets of NMR spectra. The ligand picolinate is chosen to exemplify our working method, but conclusions are drawn from all systems, reviewing trends and common features. An overview of all systems is given in two tables, including e.g. types and number of species formed. Previously unpublished modelling results at physiological conditions are also shown for all peroxovanadate-ligand systems.
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| 6. |
- Hersleth, HP, et al.
(författare)
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Structures of the high-valent metal-ion haem-oxygen intermediates in peroxidases, oxygenases and catalases
- 2006
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Ingår i: Journal of Inorganic Biochemistry. - : Elsevier BV. - 1873-3344 .- 0162-0134. ; 100:4, s. 460-476
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Forskningsöversikt (refereegranskat)abstract
- Peroxidases, oxygenases and catalases have similar high-valent metal-ion intermediates in their respective reaction cycles. In this review, haem-based examples will be discussed. The intermediates of the haem-containing enzymes have been extensively studied for many years by different spectroscopic methods like UV-Vis, EPR (electron paramagnetic resonance), resonance Raman, Mossbauer and MCD (magnetic circular dichroism). The first crystal structure of one of these high-valent intermediates was on cytochrome c peroxidase in 1987. Since then, structures have appeared for catalases in 1996, 2002, 2003, putatively for cytochrome P450 in 2000, for myoglobin in 2002, for horseradish peroxidase in 2002 and for cytochrome c peroxidase again in 1994 and 2003. This review will focus on the most recent structural investigations for the different intermediates of these proteins. The structures of these intermediates will also be viewed in light of quantum mechanical (QM) calculations on haem models. In particular quantum refinement, which is a combination of QM calculations and crystallography, will be discussed. Only small structural changes accompany the generation of these intermediates. The crystal structures show that the compound I state, with a so called pi-cation radical on the haem group, has a relatively short iron-oxygen bond (1.67-1.76 A) in agreement with a double-bond character, while the compound 11 state or the compound I state with a radical on an amino acid residue have a relatively long iron-oxygen bond (1.86-1.92 angstrom) in agreement with a single-bond character where the oxygen-atom is protonated.
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| 7. |
- Jensen, Kasper
(författare)
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Iron-sulfur clusters: Why iron?
- 2006
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Ingår i: Journal of Inorganic Biochemistry. - : Elsevier BV. - 1873-3344 .- 0162-0134. ; 100:8, s. 1436-1439
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Tidskriftsartikel (refereegranskat)abstract
- This communication addresses a simple question by means of density functional calculations: Why is iron used as the metal in. iron-sulfur clusters? While there may be several answers to this question, it is shown here that one feature - the well-defined inner-sphere reorganization energy of self-exchange electron transfer - is very much favored in iron-sulfur clusters as opposed to metal substituted analogues of Mn, Co, Ni, and Cu. Furthermore, the conclusion holds for both 1Fe and 2Fe type iron-sulfur clusters. The results show that only iron provides a small inner-sphere reorganization energy of 21 kJ/mol in 1Fe (rubredoxin) and 46 kJ/mol in 2Fe (ferredoxin) models, whereas other metal ions exhibit values in the range 57-135 kJ/mol (1Fe) and 94-140 kJ/mol (2Fe). This simple result provides an important, although partial, explanation why iron alone is used in this type of clusters. The results can be explained by simple orbital rules of electron transfer, which state that the occupation of anti-bonding orbitals should not change during the redox reactions. This rule immediately suggests good and poor electron carriers. (c) 2006 Elsevier Inc. All rights reserved.
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| 8. |
- Jensen, Kasper, et al.
(författare)
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O2-binding to heme: electronic structure and spectrum of oxyheme, studied by multiconfigurational methods
- 2005
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Ingår i: Journal of Inorganic Biochemistry. - : Elsevier BV. - 1873-3344 .- 0162-0134. ; 99:1, s. 45-54
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Tidskriftsartikel (refereegranskat)abstract
- We have studied the ground state of a realistic model of oxyheme with multiconfigurational second-order perturbation theory (CASPT2). Our results show that the ground-state electronic structure is strongly multiconfigurational in character. Thus, the wavefunction is a mixture of many different configurations, of which the three most important ones are approximately 1FeII–1O2 (70%), (12%) and 3FeII–3O2 (3%). Thus, the wavefunction is dominated by closed-shell configurations, as suggested by Pauling, whereas the Weiss configuration is not encountered among the 10 most important configurations. However, many other states are also important for this multiconfigurational wavefunction. Moreover, the traditional view is based on an oversimplified picture of the atomic-orbital contributions to the molecular orbitals. Thus, the population analysis indicates that all five iron orbitals are significantly occupied (by 0.5–2.0 electrons) and that the total occupation is most similar to the 3FeII–3O2 picture. The net charge on O2 is small, −0.20 e. Thus, it is quite meaningless to discuss which is the best valence-bond description of this inherently multiconfigurational system. Finally, we have calculated the eleven lowest ligand-field excited states of oxyheme and assigned the experimental spectrum of oxyhemoglobin with an average error of 0.24 eV.
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| 9. |
- Li, Minna, 1978, et al.
(författare)
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Synthesis and DNA threading properties of quaternary ammonium Ru(phen)(2)(dppz) (2+) derivatives
- 2009
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Ingår i: Journal of Inorganic Biochemistry. - : Elsevier BV. - 1873-3344 .- 0162-0134. ; 103:7, s. 963-970
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Tidskriftsartikel (refereegranskat)abstract
- Ruthenium complexes with one dipyrido[3,2-a:2'-3'-c]phenazine (dppz) ligand, e.g. [Ru(phen)(2)(dppz)](2+) (phen = phenanthroline), shows strong binding to double helical DNA and are well-known DNA "light-switch" molecules. We have here investigated four new [Ru(phen)(2)(dppz)](2+) derivatives with different bulky quaternary ammonium substituents on the dppz ligand to find relationships between molecular structure and intercalation kinetics, which is considered to be of importance for antitumor applicability. Linear dichroism spectroscopy shows that the enantiomers of the new complexes exhibit very similar binding geometries (intercalation of dppz moiety between adjacent DNA base pairs) as the enantiomers of the parent [Ru(phen)(2)(dppz)](2+) complex. Absorption spectra and luminescence properties provide further evidence for a final intercalative binding mode which has to be reached by threading of a bulky moiety between the strands of the DNA. Delta-enantiomers of all the new complexes show much slower association and dissociation kinetics than that of a reference complex without a cationic substituent. Kinetics were not very different whether the bulky quaternary group was derived from hexamethylene tetramine or 1,4-diazabicyclo-(2,2,2)octane (DABCO) or whether it had one or two positive charges. However, a complex in which the hexamethylene tetramine substituent is attached via a phenyl group showed a lowered association rate, in addition to an improved quantum yield of luminescence. A second positive charge on the DABCO substituent resulted in a much slower dissociation rate, suggesting that the distance from the Ru-centre and the amount of charge are both important for threading intercalation kinetics.
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| 10. |
- Li, Ping, et al.
(författare)
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FeFe -Hydrogenase active site models with relatively low reduction potentials : Diiron dithiolate complexes containing rigid bridges
- 2008
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Ingår i: Journal of Inorganic Biochemistry. - : Elsevier BV. - 0162-0134 .- 1873-3344. ; 102:4, s. 952-959
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Tidskriftsartikel (refereegranskat)abstract
- Three diiron dithiolate complexes containing rigid and conjugated bridges, [mu-SC6H4-2-(CO)S-mu]Fe-2(CO)(6) (1), [2-mu-SC5H3N-3-(CO)S-mu]Fe-2(CO)(6) (2). and the PPh3-monosubstituted complex [mu-SC6H4-2-(CO)S-mu]Fe-2(CO)(5)(PPh3) (1-P), were prepared as biomimetic models for the [FeFe]-hydrogenase active site. The structures of complexes 1 and 2 were determined by single crystal X-ray analysis, which shows that each complex features a rigid coplanar dithiolate bridge with a 2-3 degrees deviation from the bisect plane of the molecule. The influence of the rigid bridge on the reduction potentials of complexes 1, 2 and 1-P was investigated by electrochemistry. The cyclic voltammograms of complexes 1 and 2 display large positive shifts for the primary reduction potentials, that is, 380-480 mV in comparison to that of the pdt-bridged (pdt = propane-1,3-dithiolato) complex (mu-pdt)Fe-2(CO)(6) and 160-260 mV to that of the bdt-bridged (bdt = benzene- 1,2-dithiolato) analogue ([mu-bdt)Fe-2(CO)(6).
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