scholarly journals Structural insight into the Staphylococcus aureus ATP-driven exporter of virulent peptide toxins

2020 ◽  
Vol 6 (40) ◽  
pp. eabb8219
Author(s):  
N. Zeytuni ◽  
S. W. Dickey ◽  
J. Hu ◽  
H. T. Chou ◽  
L. J. Worrall ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bound State ◽  
Broad Spectrum Antibiotic ◽  
X Ray ◽  
X Ray Crystallography ◽  
Open Conformation ◽  
Mechanistic Insight ◽  
Cytolytic Peptides ◽  
Peptide Toxins ◽  
Insight Into

Staphylococcus aureus is a major human pathogen that has acquired alarming broad-spectrum antibiotic resistance. One group of secreted toxins with key roles during infection is the phenol-soluble modulins (PSMs). PSMs are amphipathic, membrane-destructive cytolytic peptides that are exported to the host-cell environment by a designated adenosine 5′-triphosphate (ATP)–binding cassette (ABC) transporter, the PSM transporter (PmtABCD). Here, we demonstrate that the minimal Pmt unit necessary for PSM export is PmtCD and provide its first atomic characterization by single-particle cryo-EM and x-ray crystallography. We have captured the transporter in the ATP-bound state at near atomic resolution, revealing a type II ABC exporter fold, with an additional cytosolic domain. Comparison to a lower-resolution nucleotide-free map displaying an “open” conformation and putative hydrophobic inner chamber of a size able to accommodate the binding of two PSM peptides provides mechanistic insight and sets the foundation for therapeutic design.

scholarly journals Rational synthesis of an atomically precise carboncone under mild conditions

2019 ◽  
Vol 5 (8) ◽  
pp. eaaw0982 ◽  
Author(s):  
Zheng-Zhong Zhu ◽  
Zuo-Chang Chen ◽  
Yang-Rong Yao ◽  
Cun-Hao Cui ◽  
Shu-Hui Li ◽  
...  
Keyword(s):  
Apex Angle ◽  
Facile Synthesis ◽  
Reaction Conditions ◽  
X Ray ◽  
Carbon Allotropes ◽  
X Ray Crystallography ◽  
Mild Conditions ◽  
Research Opportunity ◽  
Insight Into ◽  
Structural Strain

Carboncones, a special family of all-carbon allotropes, are predicted to have unique properties that distinguish them from fullerenes, carbon nanotubes, and graphenes. Owing to the absence of methods to synthesize atomically well-defined carboncones, however, experimental insight into the nature of pure carboncones has been inaccessible. Herein, we describe a facile synthesis of an atomically well-defined carboncone[1,2] (C70H20) and its soluble penta-mesityl derivative. Identified by x-ray crystallography, the carbon skeleton is a carboncone with the largest possible apex angle. Much of the structural strain is overcome in the final step of converting the bowl-shaped precursor into the rigid carboncone under mild reaction conditions. This work provides a research opportunity for investigations of atomically precise single-layered carboncones having even higher cone walls and/or smaller apex angles.

How big is big? Separation by conventional methods, X-ray and electronic structures of positional isomers of bis-tert-butylisocyano adduct of 2(3),9(10),16(17),23(24)-tetrachloro-3(2),10(9),17(16),24(23)-tetra(2,6-di-iso-propylphenoxy)-phthalocyaninato iron(II) complex

2016 ◽  
Vol 20 (01n04) ◽  
pp. 337-351 ◽  
Author(s):  
Derrick R. Anderson ◽  
Pavlo V. Solntsev ◽  
Hannah M. Rhoda ◽  
Victor N. Nemykin
Keyword(s):  
Electronic Structures ◽  
Density Functional ◽  
Positional Isomers ◽  
Excitation Energies ◽  
Functional Theory ◽  
X Ray ◽  
Vertical Excitation ◽  
X Ray Crystallography ◽  
Tddft Calculations ◽  
Insight Into

A presence of bulky 2,6-di-iso-propylphenoxy groups in bis-tert-butylisocyano adduct of 2(3),9(10),16(17),23(24)-tetrachloro-3(2),10(9),17(16),24(23)-tetra(2,6-di-iso-propylphenoxy)-phthalocyaninato iron(II) complex allows separation of two individual positional isomers and a mixture of the remaining two isomers using conventional chromatography. X-ray structures of “[Formula: see text]” and “[Formula: see text]” isomers were confimed by X-ray crystallography. Density functional theory (DFT) and time-dependent DFT (TDDFT) calculations of each individual positional isomer allowed insight into their electronic structures and vertical excitation energies, which were correlated with the experimental UV-vis and MCD spectra.

Preparation, Characterisation, Crystal Structure and Antibacterial Activity of two Bis-Schiff Bases Containing a Piperazine Ring

2018 ◽  
Vol 42 (10) ◽  
pp. 512-514
Author(s):  
Rui-bo Xu ◽  
Xiao-tian Yang ◽  
Hai-nan Li ◽  
Peng-cheng Zhao ◽  
Jiao-jiao Li ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Antibacterial Activity ◽  
Bacillus Subtilis ◽  
Schiff Bases ◽  
Piperazine Ring ◽  
X Ray ◽  
X Ray Crystallography ◽  
Good Antibacterial Activity

Two new bis-Schiff bases containing a piperazine ring, N,N‘-bis(4-chlorobenzylidene)- and N,N‘-bis(4-cyanobenzylidene)-1,4-bis(3-aminopropyl)piperazine, were prepared by the reaction of N,N‘-bis(3-aminopropyl)piperazine with 4-chloro- and 4-cyanobenzaldehyde, respectively. The dichloro compound was fully identified by X-ray crystallography and it exhibited good antibacterial activity against Escherichia coli, Staphylococcus aureus and Bacillus subtilis.

scholarly journals PHF13 is a molecular reader and transcriptional co-regulator of H3K4me2/3

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Ho-Ryun Chung ◽  
Chao Xu ◽  
Alisa Fuchs ◽  
Andreas Mund ◽  
Martin Lange ◽  
...  
Keyword(s):  
Dna Damage Response ◽  
Size Exclusion ◽  
X Ray ◽  
Chip Sequencing ◽  
X Ray Crystallography ◽  
Genome Wide ◽  
Damage Response ◽  
Exclusion Chromatography ◽  
Insight Into ◽  
Binding Cell

PHF13 is a chromatin affiliated protein with a functional role in differentiation, cell division, DNA damage response and higher chromatin order. To gain insight into PHF13's ability to modulate these processes, we elucidate the mechanisms targeting PHF13 to chromatin, its genome wide localization and its molecular chromatin context. Size exclusion chromatography, mass spectrometry, X-ray crystallography and ChIP sequencing demonstrate that PHF13 binds chromatin in a multivalent fashion via direct interactions with H3K4me2/3 and DNA, and indirectly via interactions with PRC2 and RNA PolII. Furthermore, PHF13 depletion disrupted the interactions between PRC2, RNA PolII S5P, H3K4me3 and H3K27me3 and resulted in the up and down regulation of genes functionally enriched in transcriptional regulation, DNA binding, cell cycle, differentiation and chromatin organization. Together our findings argue that PHF13 is an H3K4me2/3 molecular reader and transcriptional co-regulator, affording it the ability to impact different chromatin processes.

scholarly journals Role of Computational Methods in Going beyond X-ray Crystallography to Explore Protein Structure and Dynamics

2018 ◽  
Vol 19 (11) ◽  
pp. 3401 ◽  
Author(s):  
Ashutosh Srivastava ◽  
Tetsuro Nagai ◽  
Arpita Srivastava ◽  
Osamu Miyashita ◽  
Florence Tama
Keyword(s):  
Protein Dynamics ◽  
Computational Methods ◽  
Protein Structures ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
X Ray ◽  
X Ray Crystallography ◽  
Insight Into

Protein structural biology came a long way since the determination of the first three-dimensional structure of myoglobin about six decades ago. Across this period, X-ray crystallography was the most important experimental method for gaining atomic-resolution insight into protein structures. However, as the role of dynamics gained importance in the function of proteins, the limitations of X-ray crystallography in not being able to capture dynamics came to the forefront. Computational methods proved to be immensely successful in understanding protein dynamics in solution, and they continue to improve in terms of both the scale and the types of systems that can be studied. In this review, we briefly discuss the limitations of X-ray crystallography in studying protein dynamics, and then provide an overview of different computational methods that are instrumental in understanding the dynamics of proteins and biomacromolecular complexes.

Electronic Insight into an Antithrombotic Agent by High-Resolution X-Ray Crystallography

2001 ◽  
Vol 40 (2) ◽  
pp. 355-359 ◽  
Author(s):  
Ralf Flaig ◽  
Tibor Koritsánszky ◽  
Rainer Soyka ◽  
Ludger Häming ◽  
Peter Luger
Keyword(s):  
High Resolution ◽  
Antithrombotic Agent ◽  
X Ray ◽  
X Ray Crystallography ◽  
Insight Into

scholarly journals The Combination of X-Ray Crystallography and Cryo-Electron Microscopy Provides Insight into the Overall Architecture of the Dodecameric Rvb1/Rvb2 Complex

PLoS ONE ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. e0146457 ◽  
Author(s):  
Noella Silva-Martin ◽  
María I. Daudén ◽  
Sebastian Glatt ◽  
Niklas A. Hoffmann ◽  
Panagiotis Kastritis ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
X Ray ◽  
X Ray Crystallography ◽  
Cryo Electron Microscopy ◽  
Insight Into

scholarly journals Structure and mechanism of ATP-binding cassette transporters

2008 ◽  
Vol 364 (1514) ◽  
pp. 239-245 ◽  
Author(s):  
Kaspar P Locher
Keyword(s):  
Abc Transporters ◽  
Integral Membrane Proteins ◽  
Atp Binding ◽  
X Ray ◽  
X Ray Crystallography ◽  
Binding Domains ◽  
Mechanistic Insight ◽  
Future Challenges ◽  
Hydrolysis Of ◽  
Atp Binding Cassette

ATP-binding cassette (ABC) transporters constitute a large superfamily of integral membrane proteins that includes both importers and exporters. In recent years, several structures of complete ABC transporters have been determined by X-ray crystallography. These structures suggest a mechanism by which binding and hydrolysis of ATP by the cytoplasmic, nucleotide-binding domains control the conformation of the transmembrane domains and therefore which side of the membrane the translocation pathway is exposed to. A basic, conserved two-state mechanism can explain active transport of both ABC importers and ABC exporters, but various questions remain unresolved. In this article, I will review some of the crystal structures and the mechanistic insight gained from them. Future challenges for a better understanding of the mechanism of ABC transporters will be outlined.

scholarly journals A new on-axis multimode spectrometer for the macromolecular crystallography beamlines of the Swiss Light Source

2009 ◽  
Vol 16 (2) ◽  
pp. 173-182 ◽  
Author(s):  
Robin L. Owen ◽  
Arwen R. Pearson ◽  
Alke Meents ◽  
Pirmin Boehler ◽  
Vincent Thominet ◽  
...  
Keyword(s):  
Light Source ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
X Ray ◽  
X Ray Crystallography ◽  
Additional Information ◽  
Swiss Light Source ◽  
Induced Changes ◽  
Insight Into

X-ray crystallography at third-generation synchrotron sources permits tremendous insight into the three-dimensional structure of macromolecules. Additional information is, however, often required to aid the transition from structure to function. In situ spectroscopic methods such as UV–Vis absorption and (resonance) Raman can provide this, and can also provide a means of detecting X-ray-induced changes. Here, preliminary results are introduced from an on-axis UV–Vis absorption and Raman multimode spectrometer currently being integrated into the beamline environment at X10SA of the Swiss Light Source. The continuing development of the spectrometer is also outlined.

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