Search results for "Protein structure"
showing 10 items of 757 documents
New insights into the mechanism of action of pyrazolo[1,2-a]benzo[1,2,3,4]tetrazin-3-one derivatives endowed with anticancer potential
2018
Due to the scarce biological profile, the pyrazolo[1,2-a]benzo[1,2,3,4]tetrazine-3-one scaffold (PBT) has been recently explored as promising core for potential anticancer candidates. Several suitably decorated derivatives (PBTs) exhibited antiproliferative activity in the low-micromolar range associated with apoptosis induction and cell cycle arrest on S phase. Herein, we selected the most active derivatives and submitted them to further biological explorations to deepen the mechanism of action. At first, a DNA targeting is approached by means of flow Linear Dichroism experiments so as to evaluate how small planar molecules might interact with DNA, including the interference with the catal…
Design, synthesis, and biological evaluation of a new class of benzo[b]furan derivatives as antiproliferative agents, with in silico predicted antitu…
2018
A new series of 3-benzoylamino-5-(1H-imidazol-4-yl)methylaminobenzo[b]furans were synthesized and screened as antitumor agents. As a general trend, tested compounds showed concentration-dependent antiproliferative activity against HeLa and MCF-7 cancer cell lines, exhibiting GI50 values in the low micromolar range. In most cases, insertion of a methyl substituent on the imidazole moiety improved the antiproliferative activity. Therefore, methyl-imidazolyl-benzo[b]furans compounds were tested in cell cycle perturbation experiments, producing cell cycle arrest with proapoptotic effects. Their core similarity to known colchicine binding site binders led us to further study the structure featur…
A community resource of experimental data for NMR / X-ray crystal structure pairs
2015
We have developed an online NMR / X-ray Structure Pair Data Repository. The NIGMS Protein Structure Initiative (PSI) has provided many valuable reagents, 3D structures, and technologies for structural biology. The Northeast Structural Genomics Consortium was one of several PSI centers. NESG used both X-ray crystallography and NMR spectroscopy for protein structure determination. A key goal of the PSI was to provide experimental structures for at least one representative of each of hundreds of targeted protein domain families. In some cases, structures for identical (or nearly identical) constructs were determined by both NMR and X-ray crystallography. NMR spectroscopy and X-ray diffraction …
Organization into Higher Ordered Ring Structures Counteracts Membrane Binding of IM30, a Protein Associated with Inner Membranes in Chloroplasts and …
2016
The IM30 (inner membrane-associated protein of 30 kDa), also known as the Vipp1 (vesicle-inducing protein in plastids 1), has a crucial role in thylakoid membrane biogenesis and maintenance. Recent results suggest that the protein binds peripherally to membranes containing negatively charged lipids. However, although IM30 monomers interact and assemble into large oligomeric ring complexes with different numbers of monomers, it is still an open question whether ring formation is crucial for membrane interaction. Here we show that binding of IM30 rings to negatively charged phosphatidylglycerol membrane surfaces results in a higher ordered membrane state, both in the head group and in the inn…
Proton Leakage Is Sensed by IM30 and Activates IM30-Triggered Membrane Fusion
2020
The inner membrane-associated protein of 30 kDa (IM30) is crucial for the development and maintenance of the thylakoid membrane system in chloroplasts and cyanobacteria. While its exact physiological function still is under debate, it has recently been suggested that IM30 has (at least) a dual function, and the protein is involved in stabilization of the thylakoid membrane as well as in Mg2+-dependent membrane fusion. IM30 binds to negatively charged membrane lipids, preferentially at stressed membrane regions where protons potentially leak out from the thylakoid lumen into the chloroplast stroma or the cyanobacterial cytoplasm, respectively. Here we show in vitro that IM30 membrane binding…
Ethanol Controls the Self-Assembly and Mesoscopic Properties of Human Insulin Amyloid Spherulites.
2018
Protein self-assembly into amyloid fibrils or highly hierarchical superstructures is closely linked to neurodegenerative pathologies as Alzheimer's and Parkinson's diseases. Moreover, protein assemblies also emerged as building blocks for bioinspired nanostructured materials. In both the above mentioned fields, the main challenge is to control the growth and properties of the final protein structure. This relies on a more fundamental understanding of how interactions between proteins can determine structures and functions of biomolecular aggregates. Here, we identify a striking effect of the hydration of the single human insulin molecule and solvent properties in controlling hydrophobicity/…
Cyclins B1, T1, and H differ in their molecular mode of interaction with cytomegalovirus protein kinase pUL97
2019
Human cytomegalovirus (HCMV) is a common β-herpesvirus causing life-long latent infections. HCMV replication interferes with cell cycle regulation in host cells because the HCMV-encoded cyclin-dependent kinase (CDK) ortholog pUL97 extensively phosphorylates the checkpoint regulator retinoblastoma protein. pUL97 also interacts with cyclins B1, T1, and H, and recent findings have strongly suggested that these interactions influence pUL97 substrate recognition. Interestingly, here we detected profound mechanistic differences among these pUL97-cyclin interactions. Our study revealed the following. (i) pUL97 interacts with cyclins B1 and H in a manner dependent on pUL97 activity and HCMV-specifi…
Direct observation of alpha-lactalbumin, adsorption and incorporation into lipid membrane and formation of lipid/protein hybrid structures
2019
The interaction between proteins and membranes is of great interest in biomedical and biotechnological research for its implication in many functional and dysfunctional processes. We present an experimental study on the interaction between model membranes and alpha-lactalbumin (alpha-La). alpha-La is widely studied for both its biological function and its anti-tumoral properties. We use advanced fluorescence microscopy and spectroscopy techniques to characterize alpha-La-membrane mechanisms of interaction and alpha-La-induced modifications of membranes when insertion of partially disordered regions of protein chains in the lipid bilayer is favored. Moreover, using fluorescence lifetime imag…
Photocage-initiated time-resolved solution X-ray scattering investigation of protein dimerization
2018
Photocaging in combination with X-ray solution scattering allows for the time-resolved study of protein dynamics in solution. This method is versatile and allows for accurate triggering of protein function.
19F NMR as a versatile tool to study membrane protein structure and dynamics.
2019
Abstract To elucidate the structures and dynamics of membrane proteins, highly advanced biophysical methods have been developed that often require significant resources, both for sample preparation and experimental analyses. For very complex systems, such as membrane transporters, ion channels or G-protein coupled receptors (GPCRs), the incorporation of a single reporter at a select site can significantly simplify the observables and the measurement/analysis requirements. Here we present examples using 19F nuclear magnetic resonance (NMR) spectroscopy as a powerful, yet relatively straightforward tool to study (membrane) protein structure, dynamics and ligand interactions. We summarize meth…