scholarly journals Activation of the E3 ubiquitin ligase Parkin

2015 ◽  
Vol 43 (2) ◽  
pp. 269-274 ◽  
Author(s):  
Thomas R. Caulfield ◽  
Fabienne C. Fiesel ◽  
Wolfdieter Springer
Keyword(s):  
Enzymatic Activity ◽  
Structural Model ◽  
Mitochondrial Quality Control ◽  
X Ray ◽  
Sequential Release ◽  
E2 Enzymes ◽  
Phosphatase And Tensin Homologue ◽  
Catalytic Functions ◽  
Plos Comput Biol ◽  
Conserved Residue

The PINK1 (phosphatase and tensin homologue-induced putative kinase 1)/Parkin-dependent mitochondrial quality control pathway mediates the clearance of damaged organelles, but appears to be disrupted in Parkinson's disease (PD) [Springer and Kahle (2011) Autophagy 7, 266–278]. Upon mitochondrial stress, PINK1 activates the E3 ubiquitin (Ub) ligase Parkin through phosphorylation of the Ub-like (UBL) domain of Parkin and of the small modifier Ub itself at a conserved residue [Sauvé and Gehring (2014) Cell Res. 24, 1025–1026]. Recently resolved partial crystal structures of Parkin showed a ‘closed’, auto-inhibited conformation, consistent with its notoriously weak enzymatic activity at steady state [Wauer and Komander (2013) EMBO J. 32, 2099–2112; Riley et al. (2013) Nat. Commun. 4, 1982; Trempe et al. (2013) Science 340, 1451–1455; Spratt et al. (2013) Nat. Commun. 4, 1983]. It has thus become clear that Parkin must undergo major structural rearrangements in order to unleash its catalytic functions. Recent published findings derived from X-ray structures and molecular modelling present a complete structural model of human Parkin at an all-atom resolution [Caulfield et al. (2014) PLoS Comput. Biol. 10, e1003935]. The results of the combined in silico simulations-based and experimental assay-based study indicates that PINK1-dependent Ser65 phosphorylation of Parkin is required for its activation and triggering of ‘opening’ conformations. Indeed, the obtained structures showed a sequential release of Parkin's intertwined domains and allowed docking of an Ub-charged E2 coenzyme, which could enable its enzymatic activity. In addition, using cell-based screening, select E2 enzymes that redundantly, cooperatively or antagonistically regulate Parkin's activation and/or enzymatic functions at different stages of the mitochondrial autophagy (mitophagy) process were identified [Fiesel et al. (2014) J. Cell Sci. 127, 3488–3504]. Other work that aims to pin-point the particular pathogenic dysfunctions of Parkin mis-sense mutations have been recently disseminated (Fabienne C. Fiesel, Thomas R. Caulfield, Elisabeth L. Moussaud-Lamodiere, Daniel F.A.R. Dourado, Kotaro Ogaki, Owen A. Ross, Samuel C. Flores, and Wolfdieter Springer, submitted). Such a structure–function approach provides the basis for the dissection of Parkin's regulation and a targeted drug design to identify small-molecule activators of this neuroprotective E3 Ub ligase.

Reconstructed Structure of SiO2/Si(111) Interface

1990 ◽  
Vol 208 ◽  
Author(s):  
Ichiro Hirosawa ◽  
Jun'ichiro Nizuki ◽  
Toru Tatsumi ◽  
Koichi Akimoto ◽  
Junji Matsui
Keyword(s):  
Molecular Beam ◽  
Structural Model ◽  
Oxidation Process ◽  
Grazing Incidence ◽  
Interface Structure ◽  
X Ray Diffraction ◽  
Initial Oxidation ◽  
X Ray ◽  
Diffraction Geometry ◽  
Symmetry Structure

ABSTRACTIn order to investigate the initial oxidation process Qf the Si (111) surface, we have studied the molecular beam deposited Si0 2/Si(111)-7×7 interface structure using grazing incidence X-ray diffraction geometry. We suggest a three-fold symmetry structural model composed of stacking fault layer, dimer layer and additional ordered atoms. The three-fold symmetry structure comes from the preference for oxidation in the faulted half of the 7×7 structure.

Structure determination of the stable anhydrous phase of α-lactose from X-ray powder diffraction

2005 ◽  
Vol 61 (2) ◽  
pp. 185-191 ◽  
Author(s):  
Cyril Platteau ◽  
Jacques Lefebvre ◽  
Frederic Affouard ◽  
Jean-François Willart ◽  
Patrick Derollez ◽  
...  
Keyword(s):  
Powder Diffraction ◽  
Room Temperature ◽  
Structural Model ◽  
Hydroxyl Groups ◽  
Rietveld Refinements ◽  
X Ray ◽  
Hydrogen Bond Networks ◽  
Monte Carlo Simulated Annealing ◽  
Annealing Method

The stable anhydrous form of α-lactose has been obtained by the dehydration of α-lactose monohydrate in methanol. An X-ray powder diffraction pattern was recorded at room temperature with a laboratory diffractometer equipped with an INEL curved sensitive detector CPS120. The starting structural model of this form was found by a Monte-Carlo simulated annealing method. The structure was obtained through Rietveld refinements and the minimization of crystalline energy for the localization of the H atoms of the hydroxyl groups. Soft restraints were applied to bond lengths and angles. Networks of O—H...O hydrogen bonds account for the crystalline cohesion. A comparison is made between the hydrogen-bond networks of this form and those of the monohydrate and hygroscopic anhydrous forms of α-lactose.

scholarly journals Stacking faults in β-Ga2O3 crystals observed by X-ray topography

2018 ◽  
Vol 51 (5) ◽  
pp. 1372-1377 ◽  
Author(s):  
Hirotaka Yamaguchi ◽  
Akito Kuramata
Keyword(s):  
Crystal Growth ◽  
Partial Dislocation ◽  
Structural Model ◽  
Stacking Faults ◽  
Elastic Instability ◽  
Planar Defects ◽  
X Ray ◽  
Self Energy ◽  
Unique Structural Feature ◽  
Edge Component

Planar defects in (\overline{2}01)-oriented β-Ga2O3 wafers were studied using X-ray topography. These planar defects were rectangular with dimensions of 50–150 µm, and the X-ray topography analysis revealed that they were stacking faults (SFs) enclosed by a single partial dislocation loop on the (\overline{2}01) plane. The SF formation was found to be supported by a unique structural feature of the (\overline{2}01) plane as a slip plane; the (\overline{2}01) plane consists of close-packed octahedral Ga and O layers, allowing slips to form SFs. Vacancy arrays along the b axis in the octahedral Ga layer reduce the self-energy of the edge component in the partial dislocation extending along the b axis. It is speculated that the SFs occur during the crystal growth process for unknown reasons and then recover owing to elastic instability after initially increasing in size as crystal growth proceeds. Based on this analysis, a structural model for the SFs is proposed.

scholarly journals Calculation of total scattering from a crystalline structural model based on experimental optics parameters

2020 ◽  
Vol 53 (3) ◽  
pp. 671-678 ◽  
Author(s):  
Satoshi Hiroi ◽  
Koji Ohara ◽  
Satoru Ohuchi ◽  
Yukihiro Umetani ◽  
Takashi Kozaki ◽  
...  
Keyword(s):  
Amorphous Materials ◽  
Structural Model ◽  
Direct Calculation ◽  
Structural Disorder ◽  
Optical Parameters ◽  
Diffraction Profile ◽  
Total Scattering ◽  
X Ray ◽  
Scattering Measurements ◽  
Total Structure

Total scattering measurements enable understanding of the structural disorder in crystalline materials by Fourier transformation of the total structure factor, S(Q), where Q is the magnitude of the scattering vector. In this work, the direct calculation of total scattering from a crystalline structural model is proposed. To calculate the total scattering intensity, a suitable Q-broadening function for the diffraction profile is needed because the intensity and the width depend on the optical parameters of the diffraction apparatus, such as the X-ray energy resolution and divergence, and the intrinsic parameters. X-ray total scattering measurements for CeO2 powder were performed at beamline BL04B2 of the SPring-8 synchrotron radiation facility in Japan for comparison with the calculated S(Q) under various optical conditions. The evaluated Q-broadening function was comparable to the full width at half-maximum of the Bragg peaks in the experimental total scattering pattern. The proposed calculation method correctly accounts for parameters with Q dependence such as the atomic form factor and resolution function, enables estimation of the total scattering factor, and facilitates determination of the reduced pair distribution function for both crystalline and amorphous materials.

scholarly journals Identification of inhibitors of SARS-CoV-2 3CL-Pro enzymatic activity using a small molecule in-vitro repurposing screen

2020 ◽  
Author(s):  
Maria Kuzikov ◽  
Elisa Costanzi ◽  
Jeanette Reinshagen ◽  
Francesca Esposito ◽  
Laura Vangeel ◽  
...  
Keyword(s):  
Enzymatic Activity ◽  
Small Molecules ◽  
Drug Target ◽  
Treatment Options ◽  
Cleavage Sites ◽  
X Ray ◽  
Binding Characteristics ◽  
Main Protease ◽  
Ic50 Values

Compound repurposing is an important strategy for the identification of effective treatment options against SARS-CoV-2 infection and COVID-19 disease. In this regard, SARS-CoV-2 main protease (3CL-Pro), also termed M-Pro, is an attractive drug target as it plays a central role in viral replication by processing the viral polyproteins pp1a and pp1ab at multiple distinct cleavage sites. We here report the results of a repurposing program involving 8.7 K compounds containing marketed drugs, clinical and preclinical candidates, and small molecules regarded as safe in humans. We confirmed previously reported inhibitors of 3CL-Pro, and have identified 62 additional compounds with IC50 values below 1 uM and profiled their selectivity towards Chymotrypsin and 3CL-Pro from the MERS virus. A subset of 8 inhibitors showed anti-cytopathic effect in a Vero-E6 cell line and the compounds thioguanosine and MG-132 were analysed for their predicted binding characteristics to SARS-CoV-2 3CL-Pro. The X-ray crystal structure of the complex of myricetin and SARS-Cov-2 3CL-Pro was solved at a resolution of 1.77 Angs., showing that myricetin is covalently bound to the catalytic Cys145 and therefore inhibiting its enzymatic activity.

scholarly journals Structural characterization of the N-terminal part of the MERS-CoV nucleocapsid by X-ray diffraction and small-angle X-ray scattering

2016 ◽  
Vol 72 (2) ◽  
pp. 192-202 ◽  
Author(s):  
Nicolas Papageorgiou ◽  
Julie Lichière ◽  
Amal Baklouti ◽  
François Ferron ◽  
Marion Sévajol ◽  
...  
Keyword(s):  
Structural Model ◽  
Structural Features ◽  
Terminal Region ◽  
X Ray Diffraction ◽  
Terminal Part ◽  
Multifunctional Protein ◽  
X Ray ◽  
N Protein ◽  
Intrinsically Disordered ◽  
X Ray Scattering

The N protein of coronaviruses is a multifunctional protein that is organized into several domains. The N-terminal part is composed of an intrinsically disordered region (IDR) followed by a structured domain called the N-terminal domain (NTD). In this study, the structure determination of the N-terminal region of the MERS-CoV N proteinviaX-ray diffraction measurements is reported at a resolution of 2.4 Å. Since the first 30 amino acids were not resolved by X-ray diffraction, the structural study was completed by a SAXS experiment to propose a structural model including the IDR. This model presents the N-terminal region of the MERS-CoV as a monomer that displays structural features in common with other coronavirus NTDs.

scholarly journals Interfacial Structure of Lattice Mismatched bcc(110)/bcc(110) Transition Metal Superlattices

1993 ◽  
Vol 307 ◽  
Author(s):  
Eric E. Fullerton ◽  
S. M. Mini ◽  
A. S. Bommannavar ◽  
C. H. Sowers ◽  
S. N. Ehrlich ◽  
...  
Keyword(s):  
Lattice Strain ◽  
Structural Model ◽  
Interfacial Structure ◽  
X Ray Diffraction ◽  
X Ray ◽  
Lattice Strains ◽  
The Individual ◽  
Structural Characterizations ◽  
Modulation Wavelength ◽  
Coherent Interfaces

ABSTRACTWe present structural characterizations of a series of sputtered Fe/Nb and V/Nb superlattices by high-angle x-ray diffraction. Diffraction scans were performed with the scattering vector at various angles (χ) with respect to the layers. χ=0° diffraction spectra (normal to the layers) were fitted to a general structural model to determine the (110) lattice strains, interfacial disorder and interdiffusion. χ>0° spectra probe the lattice strain of the individual layers and the in-plane interfacial coherence. Both systems form incoherent interfaces above a critical modulation wavelength (ΛC). At ΛC, the Fe/Nb system undergoes a crystalline-to-amorphous transition while the V/Nb forms in-plane coherent interfaces.

Structural Model for Ferrihydrite

Clay Minerals ◽  
1993 ◽  
Vol 28 (2) ◽  
pp. 185-207 ◽  
Author(s):  
V. A. Drits ◽  
B. A. Sakharov ◽  
A. L. Salyn ◽  
A. Manceau
Keyword(s):  
Structural Model ◽  
Structural Difference ◽  
Coherent Scattering ◽  
Close Packing ◽  
X Ray Diffraction ◽  
Actual Structure ◽  
X Ray ◽  
Cell Parameters ◽  
Super Cell ◽  
Mean Dimension

AbstractThe structure of 6-line and 2-line ferrihydrite (Fh) has been reconsidered. X-ray diffraction (XRD) curves were first simulated for the different structural models so far proposed, and it is shown that neither of these corresponds to the actual structure of ferrihydrite. On the basis of agreement between experimental and simulated XRD curves it is shown that Fh is a mixture of three components: (i) Defect-free Fh consisting of anionic ABACA . . . close packing in which Fe atoms occupy only octahedral sites with 50% probability; the hexagonal unit-cell parameters are a = 2-96 Å and c = 9-40 Å, and the space group is P1c. (ii) Defective Fh in which Ac1Bc2A and Ab1Cb2A structural fragments occur with equal probability and alternate completely at random; Fe atoms within each of these fragments have identical ordered distribution with in the hexagonal super-cell with a = 5.26 Å. (iii) Ultradispersed hematite with mean dimension of coherent scattering domains (CSD) of 10-20 Å. The main structural difference between 6-line and 2-line Fh is the size of their CSD which is extremely small for the latter structure. Nearest Fe-Fe distances calculated for this new structural model are very close to those determined by EXAFS spectroscopy on the same samples.

scholarly journals Structural Refinement and Density Functional Theory Study of Synthetic Ge-Akaganéite (β-FeOOH)

Crystals ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 239
Author(s):  
Donghoon Chung ◽  
Changyun Park ◽  
Woohyun Choi ◽  
Yungoo Song
Keyword(s):  
Density Functional Theory ◽  
Density Functional ◽  
Structural Model ◽  
Dispersion Correction ◽  
Chemical Formula ◽  
Structural Refinement ◽  
X Ray Diffraction ◽  
Functional Theory ◽  
X Ray ◽  
Twisted Cube

In this study, we propose a revised structural model for highly ordered synthetic Ge-akaganéite, a stable analogue of tunnel-type Fe-oxyhydroxide, based on the Rietveld refinement of synchrotron X-ray diffraction data and density functional theory with dispersion correction (DFT-D) calculations. In the proposed crystal structure of Ge-akaganéite, Ge is found not only in the tunnel sites as GeO(OH)3− tetrahedra, but also 4/5 of total Ge atoms are in the octahedral sites substituting 1/10 of Fe. In addition, the tunnel structures are stabilized by the presence of hydrogen bonds between the framework OH and Cl− species, forming a twisted cube structure and the GeO(OH)3− tetrahedra corner oxygen, forming a conjugation bond. The chemical formula of the synthetic Ge-akaganéite was determined to be (Fe7.2Ge0.8)O8.8(OH)7.2Cl0.8(Ge(OH)4)0.2.

scholarly journals Detailed Molecular and Structural Analysis of Dual Emitter IrQ(ppy)2 Complex

Materials ◽  
2020 ◽  
Vol 13 (7) ◽  
pp. 1617
Author(s):  
Iulia Corina Ciobotaru ◽  
Daniel Nicolae Crisan ◽  
Primoz Šket ◽  
Constantin Claudiu Ciobotaru ◽  
Silviu Polosan
Keyword(s):  
Organometallic Compound ◽  
High Performance ◽  
Structural Model ◽  
Chemical Yield ◽  
Interatomic Distances ◽  
X Ray ◽  
Metal Ligands ◽  
Final Compound ◽  
X Ray Absorption ◽  
Detailed Molecular Analysis

The molecular structure of the 8-hydroxyquinoline–bis (2-phenylpyridyl) iridium (IrQ(ppy)2) dual emitter organometallic compound is determined based on detailed 1D and 2D nuclear magnetic resonance (NMR), to identify metal-ligands coordination, isomerization and chemical yield of the desired compound. Meanwhile, the extended X-ray absorption fine structure (EXAFS) was used to determine the interatomic distances around the iridium ion. From the NMR results, this compound IrQ(ppy)2 exhibits a trans isomerization with a distribution of coordinated N-atoms in a similar way to facial Ir(ppy)3. The EXAFS measurements confirm the structural model of the IrQ(ppy)2 compound where the oxygen atoms from the quinoline ligands induce the splitting of the next-nearest neighboring C in the second shell of the Ir3+ ions. The high-performance liquid chromatography (HPLC), as a part of the detailed molecular analysis, confirms the purity of the desired IrQ(ppy)2 organometallic compound as being more than 95%, together with the progress of the chemical reactions towards the final compound. The theoretical model of the IrQ(ppy)2, concerning the expected bond lengths, is compared with the structural model from the EXAFS and XRD measurements.

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