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331.
The mutants at position 242 of manganese peroxidase (MnP), where the native Asp has been substituted with a Ser or a Glu, have been shown to be active, and are here characterized by electronic, EPR, and NMR spectroscopies. We have also mutated another residue on the proximal side, Phe 190 to Val and Leu, yielding active mutants. When studied by the above-mentioned spectroscopies, the mutants at both positions 242 and 190 exhibit three pH-dependent transitions. In contrast to the transitions observed at low and high pH, the spectroscopic studies reveal that the transition at intermediate pH has pK(a) values up to 2 units lower for the mutants at D242E and -S and F190V than for the wild type. This process is due to the ionization of a group that affects the transition to the bis-histidine coordination at the iron. The observed changes in the pK(a) values are related to the altered affinity of the calcium-binding site in the distal pocket. Other variations are observed in the other two pK(a) values. Characterization of the cyanide derivatives indicates that the location and orientation of the distal and proximal His residues are essentially identical to that in the wild type. Our results indicate that mutations on the proximal side residues can affect changes in the distal side. In particular, deprotonation of a group, whose pK(a) is influenced by the nature of the residues in the proximal side, produces a movement of helix B, which in turn induces the coordination of the distal His and the loss of the distal calcium ion. 相似文献
332.
I Bertini C Luchinat L Messori R Monnanni A Scozzafava 《The Journal of biological chemistry》1986,261(3):1139-1146
Cobalt(II) ovotransferrin bicarbonate and oxalate ternary complexes were prepared and investigated in the pH range 7-10.5. Cobalt(II) provides an excellent and unique spectroscopic probe to monitor subtle structural differences in solution between the two sites of ovotransferrin and to investigate the structural dependence on pH. CD spectroscopy on one side and 1H NMR spectroscopy of isotropically shifted signals on the other are extremely sensitive techniques and are particularly suited for high spin cobalt(II)-containing compounds. In the case of the oxalate derivative the metal-binding ability of the protein is different at the two binding sites and is pH dependent; the CD spectra reveal two different sites, one of which is clearly pH dependent with a pKa of 9.5. On the contrary the bicarbonate analogue does not show any spectral difference between the two sites; both of them change with pH, the pKa being again 9.5. 1H NMR spectra of the oxalate derivatives at pH 7-8 reveal the presence of conformers, the distribution of which depends on the H2O/D2O ratio. Such conformers are not revealed in the bicarbonate system; at pH around 10 the NMR spectra of both systems show inequivalence between the two sites and/or the presence of different conformers for each site. Such differences are discussed in terms of the possible implications in mechanism and function. The overall spectral data are consistent with the donor groups being two histidines, two tyrosines, the synergistic anion, and possibly a solvent molecule. 相似文献
333.
Arnesano F Balatri E Banci L Bertini I Winge DR 《Structure (London, England : 1993)》2005,13(5):713-722
Cox17 is a key mitochondrial copper chaperone involved in the assembly of cytochrome c oxidase (COX). The NMR solution structure of the oxidized apoCox17 isoform consists of a coiled-coil conformation stabilized by two disulfide bonds involving Cys(26)/Cys(57) and Cys(36)/Cys(47). This appears to be a conserved tertiary fold of a class of proteins, localized within the mitochondrial intermembrane space, that contain a twin Cys-x(9)-Cys sequence motif. An isomerization of one disulfide bond from Cys(26)/Cys(57) to Cys(24)/Cys(57) is required prior to Cu(I) binding to form the Cu(1)Cox17 complex. Upon further oxidation of the apo-protein, a form with three disulfide bonds is obtained. The reduction of all disulfide bonds provides a molten globule form that can convert to an additional conformer capable of binding up to four Cu(I) ions in a polycopper cluster. This form of the protein is oligomeric. These properties are framed within a complete model of mitochondrial import and COX assembly. 相似文献
334.
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336.
Bertini S Asso V Ghilardi E Granchi C Manera C Minutolo F Saccomanni G Bortolato A Mason J Moro S Macchia M 《Bioorganic & medicinal chemistry letters》2011,21(22):6657-6661
β-Secretase (BACE1) is widely recognized as a prime drug target for the treatment of Alzheimer's disease (AD). In this Letter, we report the synthesis and the BACE1 inhibitory activity of novel, variously substituted N-[3-(9H-carbazol-9-yl)-2-hydroxypropyl]-arylcarboxamides. The best results have been obtained with the introduction of a 4-OMe substituent (IC(50)=3.8 μM) or a 3,4-dichloro substituent (IC(50)=2.5 μM) in the amidic aromatic ring. The blood-brain barrier penetration predictions resulted to be promising for this type of compounds. To better understand the structure-activity relationships (SAR) of the new derivatives, a docking study procedure has been applied exploiting different conformational and ionic states of BACE1. 相似文献
337.
Bertini Edoardo Tornielli Giovanni Battista Pezzotti Mario Zenoni Sara 《Plant Cell, Tissue and Organ Culture》2019,137(2):239-247
Plant Cell, Tissue and Organ Culture (PCTOC) - Tissue culture systems have contributed to the massive propagation of bamboos. However, micro-propagated plants show a low percentage of rooting and... 相似文献
338.
Bernini P Bertini I Luchinat C Tenori L Tognaccini A 《Journal of proteome research》2011,10(11):4983-4992
The identification and the present wide acceptance of cardiovascular risk factors such as age, sex, hypertension, hyperlipidemia, smoking, obesity, diabetes, and physical inactivity have led to dramatic reductions in cardiovascular morbidity and mortality. However, novel risk predictors present opportunities to identify more patients at risk and to more accurately define the biochemical signature of that risk. In this paper, we present a comprehensive metabonomic analysis of 864 plasma samples from healthy volunteers, through Nuclear Magnetic Resonance (NMR) and multivariate statistical analysis (regression and classification). We have found that subjects that are classified as at high or at low risk using the common clinical markers can also be discriminated using NMR metabonomics. This discrimination is not only due to common markers (such as total cholesterol, triglycerides, LDL, HDL), but also to (p < 0.05 after Bonferroni correction) other metabolites (e.g., 3-hydroxybutyrate, α-ketoglutarate, threonine, dimethylglycine) previously not associated with cardiovascular diseases. 相似文献
339.
Sco proteins are present in all types of organisms, including the vast majority of eukaryotes and many prokaryotes. It is well established that Sco proteins in eukaryotes are involved in the assembly of the Cu(A) cofactor of mitochondrial cytochrome c oxidase; however their precise role in this process has not yet been elucidated at the molecular level. In particular, some but not all eukaryotes including humans possess two Sco proteins whose individual functions remain unclear. There is evidence that eukaryotic Sco proteins are also implicated in other cellular processes such as redox signalling and regulation of copper homeostasis. The range of physiological functions of Sco proteins appears to be even wider in prokaryotes, where Sco-encoding genes have been duplicated many times during evolution. While some prokaryotic Sco proteins are required for the biosynthesis of cytochrome c oxidase, others are most likely to take part in different processes such as copper delivery to other enzymes and protection against oxidative stress. The detailed understanding of the multiplicity of roles ascribed to Sco proteins requires the identification of the subtle determinants that modulate the two properties central to their known and potential functions, i.e. copper binding and redox properties. In this review, we provide a comprehensive summary of the current knowledge on Sco proteins gained by genetic, structural and functional studies on both eukaryotic and prokaryotic homologues, and propose some hints to unveil the elusive molecular mechanisms underlying their functions. 相似文献
340.
Bermel W Bertini I Felli IC Gonnelli L Koźmiński W Piai A Pierattelli R Stanek J 《Journal of biomolecular NMR》2012,53(4):293-301
The characterization of intrinsically disordered proteins (IDPs) by NMR spectroscopy is made difficult by the extensive spectral overlaps. To overcome the intrinsic low-resolution of the spectra the introduction of high-dimensionality experiments is essential. We present here a set of high-resolution experiments based on direct (13)C-detection which proved useful in the assignment of α-synuclein, a paradigmatic IDP. In particular, we describe the implementation of 4D HCBCACON, HCCCON, HCBCANCO, 4/5D HNCACON and HNCANCO and 3/4D HCANCACO experiments, specifically tailored for spin system identification and backbone resonances sequential assignment. The use of non-uniform-sampling in the indirect dimension and of the H-flip approach to achieve longitudinal relaxation enhancement rendered the experiments very practical. 相似文献