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Query: UNIPROT:O14944 (EPR)
 13,097 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine the factors affecting the ground-state electron configuration of low-spin Fe(III) porphyrin complexes, we have examined the (1)H NMR, (13)C NMR, and EPR spectra of a series of low-spin bis-ligated Fe(III) porphyrin complexes [Fe(Por)L(2)](+/-), in which the positions of porphyrin substituents and the coordination ability of axial ligands are different. The seven porphyrins used in this study are meso-tetraalkylporphyrins (TRP: R is propyl, cyclopropyl, or isopropyl), meso-tetraphenylporphyrin (TPP), meso-tetrakis(2,3,4,5,6-pentafluorophenyl)porphyrin, and 5,10,15,20-tetraphenyl-2,3,7,8,12,13,17,18-octaalkylporphyrins (ORTPP: R is methyl or ethyl). The porphyrin cores of TRP are more or less S(4)-ruffled depending on the bulkiness of the alkyl substituents, while those of ORTPP are highly S(4)-saddled. Three types of axial ligands are examined which have the following characteristics in ligand field theory: they are (i) strong sigma-donating imidazole (HIm), (ii) strong sigma-donating and weak pi-accepting cyanide (CN(-)), and (iii) weak sigma-donating and strong pi-accepting tert-butyl isocyanide ((t)BuNC). In the case of the bis(HIm) complexes, only the isopropyl complex, [Fe(T(i)PrP)(HIm)(2)](+), has shown the less common (d(xz), d(yz))(4)(d(xy))(1) ground state; the other six complexes have exhibited the common (d(xy))(2)(d(xz), d(yz))(3) ground state. When the axial imidazole is replaced by cyanide, even the propyl and cyclopropyl complexes have shown the (d(xz), d(yz))(4)(d(xy))(1) ground state; the TPP and ORTPP complexes have still maintained the common (d(xy))(2)(d(xz), d(yz))(3) ground state. In the case of the bis((t)()BuNC) complexes, all the complexes have shown the (d(xz), d(yz))(4)(d(xy))(1) ground state. However, the contribution of the (d(xz), d(yz))(4)(d(xy))(1) state to the electronic ground state differs from complex to complex; the (d(xz), d(yz))(4)(d(xy))(1) contribution is the largest in [Fe(T(i)PrP)((t)()BuNC)(2)](+) and the smallest in [Fe(OETPPP)((t)BuNC)(2)](+). We have then examined the electronic ground state of low-spin [Fe(OEP)((t)BuNC)(2)](+) and [Fe(ProtoIXMe(2))((t)BuNC)(2)](+); OEP and ProtoIXMe(2) represent 2,3,7,8,12,13,17,18-octaethylporphyrin and protoporphyrin-IX dimethyl ester, respectively. These porphyrins have a(1u) HOMO in contrast to the other seven porphyrins that have a(2u) HOMO. The (13)C NMR and EPR studies have revealed that the contribution of the (d(xz), d(yz))(4)(d(xy))(1) state in these complexes is as small as that in [Fe(OETPP)((t)BuNC)(2)](+). On the basis of these results, we have concluded that the low-spin iron(III) porphyrins that have (i) strong axial ligands, (ii) highly saddle shaped porphyrin rings, (iii) porphyrins with a(1u) HOMO, and (iv) electron withdrawing substituents at the meso positions tend to maintain the common (d(xy))(2)(d(xz), d(yz))(3) ground state.
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PMID:Factors affecting the electronic ground state of low-spin iron(III) porphyrin complexes. 1142 88

The binding of Cu(II) to the prion protein is investigated by computations at the B3LYP level of theory on models of the octarepeat domain of the prion protein. The models incorporate the functionality of the glycine (G) and histidine (H) residues which occur in the octarepeat domain, PHGGGWGQ. The copper complexes are designated Cu[HG] and Cu[HGGG]. Coordination to the metal via the imidazole ring of the histidine, the amide carbonyl groups, and the backbone nitrogen atom of the amide groups were examined, as well as several protonation/deprotonation states of each structure. EPR and CD titration experiments suggest that the octarepeat segments of the unstructured N-terminal domain of prion protein can bind Cu(II) in a 1:1 Cu-to-octarepeat ratio. The results identify the extent to which the Cu(II) facilitates peptide backbone deprotonation, and the propensity of binding in the forward (toward the C-terminus) direction from the anchoring histidine residue. A plausible mechanism is suggested for changing from amide O-atom to deprotonated amide N-atom coordination, and for assembly of the observed species in solutions of Cu[PrP] and truncated models of it. A structure is proposed which has the N2O2 coordination pattern for the minor component observed experimentally by EPR spectroscopy for the Cu[HGGG] model. The most stable neutral Cu[HGGG] structure found, with coordination environment N3O1, corresponds to that observed for Cu[HGGGW] and Cu[HGGG] both in the solid state and as the major component in solution at neutral pH.
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PMID:Computational studies of Cu(II)[peptide] binding motifs: Cu[HGGG] and Cu[HG] as models for Cu(II) binding to the prion protein octarepeat region. 1245 99

The human prion protein fragment PrP(106-126) is a highly fibrillogenic peptide, resistant to proteinases and toxic to neurons; it derives from the normal prion protein (PrP(C)), with which it can interact, thus inhibiting its superoxide dismutase-like activity. The same properties are also shown by the abnormal isoform of the prion protein (PrP(Sc)), and this similarity makes PrP(106-126) an interesting model for the neurotoxic action of PrP(Sc). A role for copper in PrP(106-126) aggregation and toxicity has recently been evidenced, and the interaction of terminal Lys, His and Met residues with the copper ion at neutral pH has been suggested. In order to shed more light on the complex-formation equilibria of PrP(106-126) with the copper ion, a thorough investigation has been carried out by means of several experimental techniques: potentiometry, solution calorimetry, VIS spectrophotometry, circular dichroism, EPR and NMR spectroscopy. A shorter and more soluble fragment-PrP(106-113), which lacks the hydrophobic C-terminal domain of PrP(106-126) but contains all the potential donor groups-has also been considered for the sake of comparison. The involvement of terminal amino, imidazolic and amido nitrogens in complex formation has been confirmed, while no evidence was found for the interaction of side chains of Met and Lys residues with the copper ion. Solution structures for the main complexes are suggested.
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PMID:Copper binding to the neurotoxic peptide PrP106-126: thermodynamic and structural studies. 1499 27

Much attention has been paid to the natural mechanism of silkworm spinning due to the impressive mechanical properties of the natural fibers. Our results in the present work show that the fractional changes of the conformational components in regenerated silk fibroin (SF) extracted from Bombyx mori fibers is remarkably pH- and Cu(II)-dependent as demonstrated by Cu(II) EPR, (13)C NMR, and Raman spectroscopy. Cu(II) coordination atoms in SF are changed from four nitrogens to two nitrogens and two oxygens as well as to one nitrogen and three oxygens when the pH is lowered from 8.0 to 4.0. The addition of a given amount of Cu(II) into a SF solution could induce efficiently the SF conformational fractional change from silk I, a soluble helical conformation, to silk II, an insoluble beta-sheet conformation. This behavior is strikingly similar to that seen in prion protein and amyloid beta-peptide. On the basis of the similarity in the relevant sequence in SF to the octapeptide PHGGGWGQ in PrP, we suggest that at basic and neutral pH polypeptide AHGGYSGY in SF may form a 1:1 complex with Cu(II) by coordination of imidazole N(pi) of His together with two deprotonated main-chain nitrogens from two glycine residues and one nitrogen or oxygen from serine. Such a type of coordination may make the interaction between two adjacent beta-form polypeptide chains more difficult, thereby leading to an amorphous structure. Under weakly acidic conditions, however, Cu(II)-amide linkages may be broken and Cu(II) may switch to bind two N(tau) from two histidines in adjacent peptide chains, forming an intermolecular His(N(tau))-Cu(II)-His(N(tau)) bridge. This type of coordination may induce beta-sheet formation and aggregation, leading to a crystalline structure.
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PMID:Effect of pH and copper(II) on the conformation transitions of silk fibroin based on EPR, NMR, and Raman spectroscopy. 1537 33

A chimeric Cu-binding peptide has been designed on the basis of a turn substitution of the prion (PrP) octarepeat Cu-binding site into the engrailed homeodomain helix-turn-helix motif (HTH). This system is a model for the investigation of a single PrP Cu-binding site in a defined protein context. The 28-mer Cu-HTH peptide P7 spectroscopically mimics the PrP octarepeat (P7 = TERRRQQLSHGGGWGEAQIKIWFQNKRA). The Cu(II)-binding affinity of P7 was determined by ESI-MS and tryptophan fluorescence titrations to be K(d) = 2.5 +/- 0.7 microM at pH = 7.0. The quenching of fluorescence of the Trp within the binding loop (underlined above) is pH dependent and highly specific for Cu(II). No Trp quenching was observed in the presence of divalent Zn, Mn, Co, Ni, or Ca ions, and ESI-MS titrations confirmed that these divalent ions do not appreciably bind to P7. The EPR spectrum of Cu(II)-P7 shows that the Cu environment is axial and consistent with 6-coordinate N(3)O(H(2)O)(2) or N(4)(H(2)O)(2) coordination (A( parallel) = 172 x10(-)(4) cm(-)(1); g( parallel) = 2.27), very similar to that of the PrP octarepeat itself. Also like PrP, circular dichroism studies show that apo P7 is predominantly disordered in solution, and the structure is slightly enhanced by Cu binding. These data show the Cu-PrP HTH peptide reproduces the Cu-binding behavior of a single PrP octarepeat in a new context.
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PMID:De novo design of a copper(II)-binding helix-turn-helix chimera: the prion octarepeat motif in a new context. 1561 3

1H NMR, (13)C NMR, and EPR spectra of six-coordinate ferric porphyrin complexes [Fe(Por)L2]ClO4 with different porphyrin structures are presented, where porphyrins (Por) are planar 5,10,15,20-tetraphenylporphyrin (TPP), ruffled 5,10,15,20-tetraisopropylporphyrin (TiPrP), and saddled 2,3,7,8,12,13,17,18-octaethyl-5,10,15,20-tetraphenylporphyrin (OETPP), and axial ligands (L) are weak oxygen ligands such as pyridine-N-oxide, substituted pyridine-N-oxide, DMSO, DMF, MeOH, THF, 2-MeTHF, and dioxane. These complexes exhibit the spin states ranging from an essentially pure high-spin (S = 5/2) to an essentially pure intermediate-spin (S = 3/2) state depending on the field strength of the axial ligands and the structure of the porphyrin rings. Reed and Guiset reported that the pyrrole-H chemical shift is a good probe to determine the spin state in the spin admixed S = 5/2,3/2 complexes (Reed, C. A.; Guiset, F. J. Am. Chem. Soc. 1996, 118, 3281-3282). In this paper, we report that the chemical shifts of the alpha- and beta-pyrrole carbons can also be good probes to determine the spin state because they have shown good correlation with those of the pyrrole-H or pyrrole-C(alpha). By putting the observed or assumed pyrrole-H or pyrrole-C(alpha) chemical shifts of the pure high-spin and pure intermediate-spin complexes into the correlation equations, we have estimated the carbon chemical shits of the corresponding complexes. The orbital interactions between iron(III) and porphyrin have been examined on the basis of these chemical shifts, from which we have found that both the d(xy)-a(2u) interaction in the ruffled Fe(T(i)PrP)L2+ and d(xy)-a(1u) interaction in the saddled Fe(OETPP)L2+ are quite weak in the high-spin and probably in the intermediate-spin complexes as well. Close inspection of the correlation lines has suggested that the electron configuration of an essentially pure intermediate-spin Fe(T(i)PrP)L2+ changes from (d(xy), d(yz))3(d(xy))1(d(z)2)1 to (d(xy))2(d(xz), d(yz))2(d(z)2)1 as the axial ligand (L) changes from DMF to MeOH, THF, 2-MeTHF, and then to dioxane. Although the DFT calculation has indicated that the highly saddled intermediate-spin Fe(OETPP)(THF)2+ should adopt (d(xy), d(yz))3(d(xy))1(d(z)2)1 rather than (d(xy))2(d(xz), d(yz))2(d(z)2)1 because of the strong d(xy)-a(1u) interaction (Cheng, R.-J.; Wang, Y.-K.; Chen, P.-Y.; Han, Y.-P.; Chang, C.-C. Chem. Commun. 2005, 1312-1314), our 13C NMR study again suggests that Fe(OETPP)(THF)2+ should be represented as (d(xy))2(d(xz), d(yz))2(d(z)2)1 because of the weak d(xy)-a(1u) interaction. The contribution of the S = 3/2 state in all types of the spin admixed S = 5/2,3/2 six-coordinate complexes has been determined on the basis of the (13)C NMR chemical shifts.
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PMID:Electronic structures of six-coordinate ferric porphyrin complexes with weak axial ligands: usefulness of 13C NMR chemical shifts. 1621 60

A natively unfolded region of the prion protein, PrP(90-126) binds Cu(2+) ions and is vital for prion propagation. Pentapeptides, acyl-GGGTH(92-96) and acyl-TNMKH(107-111), represent the minimum motif for this Cu(2+) binding region. EPR and (1)H NMR suggests that the coordination geometry for the two binding sites is very similar. However, the visible CD spectra of the two sites are very different, producing almost mirror image spectra. We have used a series of analogues of the pentapeptides containing His(96) and His(111) to rationalise these differences in the visible CD spectra. Using simple histidine-containing tri-peptides we have formulated a set of empirical rules that can predict the appearance of Cu(2+) visible CD spectra involving histidine and amide main-chain coordination.
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PMID:Empirical rules for rationalising visible circular dichroism of Cu2+ and Ni2+ histidine complexes: applications to the prion protein. 1735 79

The cellular prion protein (PrP(C)) is a copper binding protein. The molecular features of the Cu(2+) binding sites have been investigated and characterized by spectroscopic experiments on PrP(C)-derived peptides and the correctly folded human full-length PrP(C) (hPrP-[23-231]). These experiments allowed us to distinguish two different configurations of copper binding. The different copper complexes depend on sequence context, buffer conditions and stoichiometry of copper. The combined information of spectroscopic data from our EXAFS, EPR and ENDOR experiments was used to create models for these two copper complexes. A large number of conformations of these models were calculated using molecular mechanics computations, and the simulated spectra of these structures were compared with our experimental data. Common features and differences of the copper binding motifs are discussed in this paper and it remains for future investigations to study whether different configurations are associated with different functional states of PrP(C).
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PMID:The configuration of the Cu(2+) binding region in full-length human prion protein compared with the isolated octapeptide. 1748 74

Spin-probe and spin-label techniques were used to study the interactions of the Abeta 1-28 peptide involved in Alzheimer disease and the PrP 106-126 peptide suspected to be preferentially involved in spongiform encephalopathies with three different types of dendrimers. A computer-aided EPR analysis of a positively charged and a neutral spin probe was performed by comparing the pure dendrimer and peptide systems with the dendrimer-peptide ones. Also spin-labeled PAMAM dendrimers were used to test the interactions. The results show the interactions between dendrimer and peptide monomer to be stronger for Abeta 1-28 than for PrP 106-126. PAMAM dendrimers perturb the aggregation of the peptides more than PPI dendrimers do.
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PMID:EPR study of the interactions between dendrimers and peptides involved in Alzheimer's and prion diseases. 1765 61

Transmissible spongiform encephalopathies (TSEs) represent a group of fatal neurodegenerative diseases that are associated with conformational conversion of the normally monomeric and alpha-helical prion protein, PrP(C), to the beta-sheet-rich PrP(Sc). This latter conformer is believed to constitute the main component of the infectious TSE agent. In contrast to high-resolution data for the PrP(C) monomer, structures of the pathogenic PrP(Sc) or synthetic PrP(Sc)-like aggregates remain elusive. Here we have used site-directed spin labeling and EPR spectroscopy to probe the molecular architecture of the recombinant PrP amyloid, a misfolded form recently reported to induce transmissible disease in mice overexpressing an N-terminally truncated form of PrP(C). Our data show that, in contrast to earlier, largely theoretical models, the con formational conversion of PrP(C) involves major refolding of the C-terminal alpha-helical region. The core of the amyloid maps to C-terminal residues from approximately 160-220, and these residues form single-molecule layers that stack on top of one another with parallel, in-register alignment of beta-strands. This structural insight has important implications for understanding the molecular basis of prion propagation, as well as hereditary prion diseases, most of which are associated with point mutations in the region found to undergo a refolding to beta-structure.
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PMID:Molecular architecture of human prion protein amyloid: a parallel, in-register beta-structure. 1802 69


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