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71.
Lucia Banci Ivano Bertini Francesca Cantini Sayaka Inagaki Manuele Migliardi Antonio Rosato 《The Journal of biological chemistry》2010,285(4):2537-2544
We report the solution NMR structures of the N-domain of the Menkes protein (ATP7A) in the ATP-free and ATP-bound forms. The structures consist of a twisted antiparallel six-stranded β-sheet flanked by two pairs of α-helices. A protein loop of 50 amino acids located between β3 and β4 is disordered and mobile on the subnanosecond time scale. ATP binds with an affinity constant of (1.2 ± 0.1) × 104 m−1 and exchanges with a rate of the order of 1 × 103 s−1. The ATP-binding cavity is considerably affected by the presence of the ligand, resulting in a more compact conformation in the ATP-bound than in the ATP-free form. This structural variation is due to the movement of the α1-α2 and β2-β3 loops, both of which are highly conserved in copper(I)-transporting PIB-type ATPases. The present structure reveals a characteristic binding mode of ATP within the protein scaffold of the copper(I)-transporting PIB-type ATPases with respect to the other P-type ATPases. In particular, the binding cavity contains mainly hydrophobic aliphatic residues, which are involved in van der Waal''s interactions with the adenine ring of ATP, and a Glu side chain, which forms a crucial hydrogen bond to the amino group of ATP. 相似文献
72.
73.
Ghezzi P Casagrande S Massignan T Basso M Bellacchio E Mollica L Biasini E Tonelli R Eberini I Gianazza E Dai WW Fratelli M Salmona M Sherry B Bonetto V 《Proteomics》2006,6(3):817-825
Using redox proteomics techniques to characterize the thiol status of proteins in human T lymphocytes, we identified cyclophilin A (CypA) as a specifically oxidized protein early after mitogen activation. CypA is an abundantly expressed cytosolic protein, target of the immunosuppressive drug cyclosporin A (CsA), for which a variety of functions has been described. In this study, we could identify CypA as a protein undergoing glutathionylation in vivo. Using MALDI-MS we identified Cys52 and Cys62 as targets of glutathionylation in T lymphocytes, and, using bioinformatic tools, we defined the reasons for the susceptibility of these residues to the modification. In addition, we found by circular dichroism spectroscopy that glutathionylation has an important impact on the secondary structure of CypA. Finally, we suggest that glutathionylation of CypA may have biological implications and that CypA may play a key role in redox regulation of immunity. 相似文献
74.
Metalloproteins are proteins capable of binding one or more metal ions, which may be required for their biological function, or for regulation of their activities or for structural purposes. Genome sequencing projects have provided a huge number of protein primary sequences, but, even though several different elaborate analyses and annotations have been enabled by a rich and ever-increasing portfolio of bioinformatic tools, metal-binding properties remain difficult to predict as well as to investigate experimentally. Consequently, the present knowledge about metalloproteins is only partial. The present bioinformatic research proposes a strategy to answer the question of how many and which proteins encoded in the human genome may require zinc for their physiological function. This is achieved by a combination of approaches, which include: (i) searching in the proteome for the zinc-binding patterns that, on their turn, are obtained from all available X-ray data; (ii) using libraries of metal-binding protein domains based on multiple sequence alignments of known metalloproteins obtained from the Pfam database; and (iii) mining the annotations of human gene sequences, which are based on any type of information available. It is found that 1684 proteins in the human proteome are independently identified by all three approaches as zinc-proteins, 746 are identified by two, and 777 are identified by only one method. By assuming that all proteins identified by at least two approaches are truly zinc-binding and inspecting the proteins identified by a single method, it can be proposed that ca. 2800 human proteins are potentially zinc-binding in vivo, corresponding to 10% of the human proteome, with an uncertainty of 400 sequences. Available functional information suggests that the large majority of human zinc-binding proteins are involved in the regulation of gene expression. The most abundant class of zinc-binding proteins in humans is that of zinc-fingers, with Cys4 and Cys2His2 being the most common types of coordination environment. 相似文献
75.
Baig I Bertini I Del Bianco C Gupta YK Lee YM Luchinat C Quattrone A 《Biochemistry》2004,43(18):5562-5573
In the frame of a research aimed at the detailed structural characterization of human calcium-binding proteins of the EF-hand family, the solution structure of human alpha-parvalbumin has been solved by NMR and refined with the help of substitution of the Ca(2+) ion in the EF site with the paramagnetic Dy(3+) ion. A simple (1)H-(15)N HSQC spectrum allowed the NH assignments based on the properties of Dy(3+). This allowed us to exploit pseudocontact shifts and residual dipolar couplings for solution structure refinement. The backbone and heavy atom RMSD are 0.55 +/- 0.08 and 1.02 +/- 0.08 A, respectively, and decrease to 0.39 +/- 0.05 and 0.90 +/- 0.06 A upon refinement with paramagnetism-based restraints. The RMSD for the metal itself in the EF site in the refined structure is 0.26 +/- 0.12 A. Backbone NH R(1), R(2), and NOE measured at two temperatures show the protein to be relatively rigid. The NH orientations are well determined by the paramagnetism-based restraints. This allows us to detect small but significant local structural differences with the orthologue protein from rat, whose X-ray structure is available at 2.0 A resolution. All differences are related to local changes in the amino acidic composition. 相似文献
76.
77.
Lucia?Banci Ivano?BertiniEmail author Isabella?C.?Felli Ludwig?Krippahl Karel?Kubicek José?J.?G.?Moura Antonio?Rosato 《Journal of biological inorganic chemistry》2003,8(7):777-786
The interaction of reduced rabbit cytochrome b5 with reduced yeast iso-1 cytochrome c has been studied through the analysis of 1H–15N HSQC spectra, of 15N longitudinal (R1) and transverse (R2) relaxation rates, and of the solvent exchange rates of protein backbone amides. For the first time, the adduct has been investigated also from the cytochrome c side. The analysis of the NMR data was integrated with docking calculations. The result is that cytochrome b5 has two negative patches capable of interacting with a single positive surface area of cytochrome c. At low protein concentrations and in equimolar mixture, two different 1:1 adducts are formed. At high concentration and/or with excess cytochrome c, a 2:1 adduct is formed. All the species are in fast exchange on the scale of differences in chemical shift. By comparison with literature data, it appears that the structure of one 1:1 adduct changes with the origin or primary sequence of cytochrome b5.Electronic Supplementary Material Supplementary material is available for this article if you access the article at . A link in the frame on the left on that page takes you directly to the supplementary material.Abbreviations HSQC heteronuclear single quantum correlation spectroscopy - MD molecular dynamics 相似文献
78.
Molecular dynamics (MD) simulations starting from crystallographic data allowed us to directly account for the effects of the protonation state of Glu89 on the conformational stability of apo- and holo-beta-lactoglobulin (BLG). In apo-BLG simulations starting from the protonated crystal structure, we observe a long-lived H-bond interaction between the protonated Glu89 and Ser116. This interaction, sequestering the proton from the aqueous medium, explains a pK(half) value evaluated at pH 7.3 by continuum electrostatics/Monte Carlo computation on MD data, using linear response approximation. A very large root-mean-square deviation (RMSD; 5.11 A) is observed for the EF loop between protonated and unprotonated apo-BLG. This results from a quite different orientation of the EF loop that acts either as a closed or as an open lid above the protein calyx. Proton exchange by Glu89 in apo- but not in holo-BLG is associated with a reorganization energy of 4.7 kcal/mol. A 3-ns MD simulation starting from the crystal structure of protonated apo-BLG, but considering the Glu89 as unprotonated, shows the progressive opening of the lid giving rise to the Tanford transition. In both holo-BLG forms, the lid is most probably held in place by hydrophobic interactions of amino acid side-chains of the EF loop with the palmitate hydrocarbon tail. 相似文献
79.
Bertini I Felli IC Kümmerle R Luchinat C Pierattelli R 《Journal of biomolecular NMR》2004,30(3):245-251
13C-13C NOESY experiments were performed under long mixing time conditions on reduced human superoxide dismutase (32 kDa, 15N, 13C and 70% 2H labeled). 13C-13C couplings were successfully eliminated through post-processing of in-phase-anti-phase (IPAP) data. It appears that at mixing time m of 3.0 s the spin diffusion mechanism allows the detection of 96% of the two-bond correlations involving C and C. The interpretation was confirmed by simulations. This approach broadens the range of applicability of 13C-13C NOESY spectroscopy. 相似文献
80.
Susceptibility of methicillin-resistant staphylococci to oregano essential oil, carvacrol and thymol 总被引:4,自引:0,他引:4
Nostro A Blanco AR Cannatelli MA Enea V Flamini G Morelli I Sudano Roccaro A Alonzo V 《FEMS microbiology letters》2004,230(2):191-195
The aim of this study was to evaluate the susceptibility of methicillin-susceptible and methicillin-resistant staphylococci (MSS, MRS) to oregano essential oil, carvacrol and thymol. The commercial aerial parts of Origanum vulgare L. were hydrodistilled and the essential oil analysed by gas- chromatography/electron impact mass spectrometry. The inhibition efficacy of this essence and its major components was assayed against 26 MSS and 21 MRS, using an agar dilution method. The methicillin resistance was thoroughly typed by Epsilometer test (E-test), polymerase chain reaction for mecA gene detection and PBP2' latex agglutination test. The results clearly demonstrated that the comparison between the susceptibility of MSS and MRS to oregano oil, carvacrol and thymol showed no significant differences (Fisher's exact test, P > 0.05). The best minimum inhibitory concentration values were reported for carvacrol (0.015-0.03%, v/v) followed by thymol (0.03-0.06%, v/v) and oregano oil (0.06-0.125%, v/v). 相似文献