Search results for "Biochemistry & Molecular Biology"
showing 10 items of 431 documents
Molecular basis of SARS-CoV-2 infection and rational design of potential antiviral agents: Modeling and simulation approaches
2020
International audience; The emergence in late 2019 of the coronavirus SARS-CoV-2 has resulted in the breakthrough of the COVID-19 pandemic that is presently affecting a growing number of countries. The development of the pandemic has also prompted an unprecedented effort of the scientific community to understand the molecular bases of the virus infection and to propose rational drug design strategies able to alleviate the serious COVID-19 morbidity. In this context, a strong synergy between the structural biophysics and molecular modeling and simulation communities has emerged, resolving at the atomistic level the crucial protein apparatus of the virus and revealing the dynamic aspects of k…
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…
Transmembrane signaling and cytoplasmic signal conversion by dimeric transmembrane helix 2 and a linker domain of the DcuS sensor kinase
2020
Transmembrane (TM) signaling is a key process of membrane-bound sensor kinases. The C4-dicarboxylate (fumarate) responsive sensor kinase DcuS of Escherichia coli is anchored by TM helices TM1 and TM2 in the membrane. Signal transmission across the membrane relies on the piston-type movement of the periplasmic part of TM2. To define the role of TM2 in TM signaling, we use oxidative Cys cross-linking to demonstrate that TM2 extends over the full distance of the membrane and forms a stable TM homodimer in both the inactive and fumarate-activated state of DcuS. An S186xxxGxxxG194 motif is required for the stability and function of the TM2 homodimer. The TM2 helix further extends on the periplas…
Directional high-throughput sequencing of RNAs without gene-specific primers.
2018
Ribosomal RNA analysis is a useful tool for characterization of microbial communities. However, the lack of broad-range primers has hampered the simultaneous analysis of eukaryotic and prokaryotic members by amplicon sequencing. We present a complete workflow for directional, primer-independent sequencing of size-selected small subunit ribosomal RNA fragments. The library preparation protocol includes gel extraction of the target RNA, ligation of an RNA oligo to the 5′-end of the target, and cDNA synthesis with a tailed random-hexamer primer and further barcoding. The sequencing results of a phytoplankton mock community showed a highly similar profile to the biomass indicators. This method…
DHA induces Jurkat T-cell arrest in G2/M phase of cell cycle and modulates the plasma membrane expression of TRPC3/6 channels.
2021
Abstract We investigated whether docosahexaenoic acid (DHA), a dietary n-3 fatty acid, modulates calcium (Ca2+) signaling and cell cycle progression in human Jurkat T-cells. Our study demonstrates that DHA inhibited Jurkat T-cell cycle progression by blocking their passage from S phase to G2/M phase. In addition, DHA decreased the plasma membrane expression of TRPC3 and TRPC6 calcium channels during T-cell proliferation. Interestingly, this fatty acid increased plasma membrane expression of TRPC6 after 24 h of mitogenic stimulation by phorbol-13-myristate-12-acetate (PMA) and ionomycin. These variations in the membrane expression of TRPC3 and TRPC6 channels were not directly correlated with…
Drug metabolism by cultured human hepatocytes: how far are we from the in vivo reality?
2004
The investigation of metabolism is an important milestone in the course of drug development. Drug metabolism is a determinant of drug pharmacokinetics variability in human beings. Fundamental to this are phenotypic differences, as well as genotypic differences, in the expression of the enzymes involved in drug metabolism. Genotypic variability is easy to identify by means of polymerase chain reaction-based or DNA chip-based methods, whereas phenotypic variability requires direct measurement of enzyme activities in liver, or, indirectly, measurement of the rate of metabolism of a given compound in vivo. There is a great deal of phenotypic variability in human beings, only a minor part being…
Identification of Novel Phosphopeptides After Simulated Digestion of αs2-casein by Tandem Mass Spectrometry
2006
Casein phosphopeptides (CPPs) are encrypted in αs1-, αs2-and β-casein (CN) and can be released by in vitro, in vivohydrolysis or food processing of dairy foods. Bovine αs2-CN contains two cluster sequences of anionic phosphoseryl and glutamyl residues SpSpSpEE in its structure (residues 8–12 and 56–63), which can modulate mineral bioavailability. In this study αs2-casein (αs2-CN) was subjected to simulated gastrointestinal digestion. CPPs released were sequenced by on-line reversed-phase high performance liquid chromatography coupled to electrospray ionisation tandem mass spectrometry (RP-HPLC-ESIMS/MS). Six novel αs2-CN derived CPPs, Three of them (αs2-CN(54–87)4P,αs2-CN(24–70)4P and αs2-…
Immunological properties of oxygen-transport proteins: hemoglobin, hemocyanin and hemerythrin
2016
It is now well documented that peptides with enhanced or alternative functionality (termed cryptides) can be liberated from larger, and sometimes inactive, proteins. A primary example of this phenomenon is the oxygen-transport protein hemoglobin. Aside from respiration, hemoglobin and hemoglobin-derived peptides have been associated with immune modulation, hematopoiesis, signal transduction and microbicidal activities in metazoans. Likewise, the functional equivalents to hemoglobin in invertebrates, namely hemocyanin and hemerythrin, act as potent immune effectors under certain physiological conditions. The purpose of this review is to evaluate the true extent of oxygen-transport protein dy…
Virus-host interactome: Putting the accent on how it changes
2017
[EN] Viral infections are extremely complex processes that could only be well understood by precisely characterizing the interaction networks between the virus and the host components. In recent years, much effort has gone in this directionwith the aimof unveiling themolecular basis of viral pathology. These networks are mostly formed by viral and host proteins, and are expected to be dynamic bothwith time and space (i.e., with the progression of infection, as well as with the virus and host genotypes; what we call plastodynamic). This largely overlooked spatio-temporal evolution urgently calls for a change both in the conceptual paradigms and experimental techniques used so far to characte…
A DFT study on the chiral synthesis of R-phenylacetyl carbinol within the quantum chemical cluster approach
2017
Abstract The reaction pathway leading to R-phenylacetyl carbinol within the quantum chemical cluster approach is addressed by means of density functional theory (DFT) calculations. The study includes calculation of Fukui functions, activation free energies, and potential energy surface scans, both in gas and solution phase. The protonation states of the nitrogen atoms of the pyrimidine moiety are determined. The reaction appears to be slightly exergonic (ΔG 0 = −5.6 and −4.0 kcal/mol for gas and solution phase, respectively) following a concerted synchronous mechanism having activation free energy barriers of 16.2 and 13.3 kcal/mol, in gas phase and solution phase, respectively.