67 research outputs found
Erratum: Mixed quantum-classical dynamics of an amide-I vibrational excitation in a protein a-helix [Phys. Rev. B 82, 174308 (2010)]
In the GROMACS codemodifications, instead of the nanometer unit for the distance that is standard in GROMACS, a unit of 1 °A was previously assumed. This led to dipole-dipole
interactions between amide I vibrations at different sites and the interaction energies of the amide I vibration with the
protein hydrogen bonds being overestimated, respectively, by three orders and by one order of magnitude
Binding modes of decavanadate to myosin and inhibition of the actomyosin ATPase activity
Decavanadate, a vanadate oligomer, is known to interact with myosin and to inhibit the ATPase activity, but the putative binding sites and the mechanism of inhibition are still to be clarified. We have previously proposed that the decavanadate (V10O28
6−) inhibition of the actin-stimulated
myosin ATPase activity is non-competitive towards both actin and ATP. A likely explanation for these results is that V10 binds to the so-called back-door at the end of the Pi-tube opposite to the nucleotide-binding site. In order to further investigate this possibility, we have carried out molecular docking simulations of the V10 oligomer on three different structures of the myosin motor domain of Dictyostelium discoideum, representing distinct states of the ATPase cycle. The results indicate a clear preference of V10 to bind at the back-door, but only on the “open”
structures where there is access to the phosphate binding-loop. It is suggested that V10 acts as a “back-door stop” blocking the closure of the 50-
kDa cleft necessary to carry out ATP-γ-phosphate hydrolysis. This provides a simple explanation to the non-competitive behavior of V10 and spurs the use of the oligomer as a tool to elucidate myosin back-door conformational changes in the process of muscle contraction
FOXO family isoforms
FOXO family of proteins are transcription factors involved in many physiological and pathological processes including cellular homeostasis, stem cell maintenance, cancer, metabolic, and cardiovascular diseases. Genetic evidence has been accumulating to suggest a prominent role of FOXOs in lifespan regulation in animal systems from hydra, C elegans, Drosophila, and mice. Together with the observation that FOXO3 is the second most replicated gene associated with extreme human longevity suggests that pharmacological targeting of FOXO proteins can be a promising approach to treat cancer and other age-related diseases and extend life and health span. However, due to the broad range of cellular functions of the FOXO family members FOXO1, 3, 4, and 6, isoform-specific targeting of FOXOs might lead to greater benefits and cause fewer side effects. Therefore, a deeper understanding of the common and specific features of these proteins as well as their redundant and specific functions in our cells represents the basis of specific targeting strategies. In this review, we provide an overview of the evolution, structure, function, and disease-relevance of each of the FOXO family members.Agencia Estatal de Investigation and the European Regional Development Fund (PID2022-136654OB-I00 financed by MCIN/AEI /10.13039/501100011033 / FEDER, UE).info:eu-repo/semantics/publishedVersio
Mixed quantum-classical dynamics of an amide-I vibrational excitation in a protein a-helix
Adenosine triphosphate sATPd is known to be the main energy currency of the living cell, and is used as a coenzyme to generate energy for many cellular processes through hydrolysis to adenosine diphosphate sADPd,although the mechanism of energy transfer is not well understood. It has been proposed that following hydrolysis of the ATP cofactor bound to a protein, up to two quanta of amide-I vibrational energy are excited and utilized to bring about important structural changes in the protein. To study whether, and how, amide-I vibrational excitations are capable of leading to protein structural changes, we have added components arising from quantum-mechanical amide-I vibrational excitations to the total energy and force terms within a moleculardynamics simulation. This model is applied to helical deca-alanine as a test case to investigate how its dynamics differs in the presence or absence of an amide-I excitation. We find that the presence of an amide-I excitation can bias the structure toward a more helical state
Structure of ß-cinnamomin, a protein toxic to some plant species
Phytophthora and Pythium species are among the most aggressive plant pathogens, as they invade many economically important crops and forest trees. They secrete large amounts
of 10 kDa proteins called elicitins that can act as elicitors of plant defence mechanisms. These proteins may also induce a
hypersensitive response (HR) including plant cell necrosis, with different levels of toxicity depending on their pI. Recent
studies showed that elicitins function as sterol carrier proteins.
The crystallographic structure of the highly necrotic recombinant -cinnamomin ( -CIN) from Phytophthora cinnamomi has been determined at 1.8 A Ê resolution using the molecularreplacement method. -CIN has the same overall structure as -cryptogein ( -CRY), an elicitin secreted by Phytophthora
cryptogea, although it shows a different surface electrostatic potential distribution. The protein was expressed in Pichia pastoris and crystallized in the triclinic space group with two monomers in the asymmetric unit. The interface formed by
these two monomers resembles that from -CRY dimer, although with fewer interactions
The Institute for Biotechnology and Bioengineering (IBB)
The Laboratório Associado Institute for Biotechnology and Bioengineering (IBB) is a
research unit aiming to be a strategic infrastructure for the development of the Portuguese
R&D and innovation policies in the areas of Biotechnology, Bioengineering, Biomaterials and
Life, Biomedical and Agricultural Sciences. IBB combines its R&D activities with advanced
higher education, technology transfer, consulting and services, with the aim of fostering the
industrial, health, agriculture and environmental sectors
Comparative analysis of zebrafish bone morphogenetic proteins 2, 4 and 16: molecular and evolutionary perspectives
BMP2, BMP4 and BMP16 form a subfamily of bone morphogenetic proteins acting as pleiotropic growth factors during development and as bone inducers during osteogenesis. BMP16 is the most recent member of this subfamily and basic data regarding protein structure and function, and spatio-temporal gene expression is still scarce. In this work, insights on BMP16 were provided through the comparative analysis of structural and functional data for zebrafish BMP2a, BMP2b, BMP4 and BMP16 genes and proteins, determined from three-dimensional models, patterns of gene expression during development and in adult tissues, regulation by retinoic acid and capacity to activate BMP-signaling pathway. Structures of Bmp2a, Bmp2b, Bmp4 and Bmp16 were found to be remarkably similar; with residues involved in receptor binding being highly conserved. All proteins could activate the BMP-signaling pathway, suggesting that they share a common function. On the contrary, stage-and tissue-specific expression of bmp2, bmp4 and bmp16 suggested the genes might be differentially regulated (e.g. different transcription factors, enhancers and/or regulatory modules) but also that they are involved in distinct physiological processes, although with the same function. Retinoic acid, a morphogen known to interact with BMP-signaling during bone formation, was shown to downregulate the expression of bmp2, bmp4 and bmp16, although to different extents. Taxonomic and phylogenetic analyses indicated that bmp16 diverged before bmp2 and bmp4, is not restricted to teleost fish lineage as previously reported, and that it probably arose from a whole genomic duplication event that occurred early in vertebrate evolution and disappeared in various tetrapod lineages through independent events
Odorant binding proteins : a biotechnological tool for odour control
The application of an odorant binding protein for odour control and fragrance delayed release from a textile surface was first explored in this work. Pig OBP-1 gene was cloned and expressed in Escherichia coli , and the purified protein was biochemically characterized. The IC50 values(concentrations of competitor that caused a decay of fluorescence to half-maximal intensity) were determined for four distinct fragrances, namely, citronellol, benzyl benzoate,citronellyl valerate and ethyl valerate. The results showed a strong binding of citronellyl valerate,citronellol and benzyl benzoate to the recombinant protein, while ethyl valerate displayed weaker binding. Cationized cotton substrates were coated with porcine odorant binding protein and tested for
their capacity to retain citronellol and to mask the smell of
cigarette smoke. The immobilized protein delayed the release
of citronellol when compared to the untreated cotton. According to a blind evaluation of 30 assessors, the smell of cigarette smoke, trapped onto the fabrics’ surface, was successfully attenuated by porcine odorant binding protein (more than 60 % identified the weakest smell intensity after protein exposure compared to β-cyclodextrin-treated and untreated cotton fabrics). This work demonstrated that porcine odorant binding protein can be an efficient solution to prevent and/orremove unpleasant odours trapped on the large surface of textiles. Its intrinsic properties make odorant binding proteins excellent candidates for controlled release systems which constitute a new application for this class of proteins.This work was co-funded by the European Social Fund through the management authority POPH and FCT. The authors Carla Silva and Teresa Matama would like to acknowledge their post-doctoral fellowships: SFRH/BPD/46515/2008 and SFRH/BPD/47555/2008, respectively
In-beam tests of the AMS RICH prototype with 20 A GeV/c secondary ions
Abstract A prototype of the AMS Cherenkov imager (RICH) has been tested by means of a low intensity 20 GeV /c per nucleon ion beam coming from the fragmentation of a primary beam of Pb ions. Data have been collected for charges
How does heparin prevent the pH inactivation of cathepsin B? Allosteric mechanism elucidated by docking and molecular dynamics
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