High-resolution crystal structure of spectrin SH3 domain fused with a proline-rich peptide

A new chimeric protein, named WT-CIIA, was designed by connecting the proline-rich decapeptide PPPVPPYSAG to the C-terminus of the alpha-spectrin SH3 domain through a natural twelve-residue linker to obtain a single-chain model that would imitate intramolecular SH3-ligand interaction. The crystal structure of this fusion protein was determined at 1.7 ? resolution. The asymmetric unit of the crystal contained two SH3 globules contacting with one PPPVPPY fragment located between them. The domains are related by the two-fold non-crystallographic axis and the ligand lies in two opposite orientations with respect to the conservative binding sites of SH3 domains.     

The L(M196)H mutation in Rhodobacter sphaeroides reaction center results in new electrostatic interactions

Photosynthesis Research - New histidine residue was introduced in M196 position in the reaction center of Rhodobacter sphaeroides in order to alter polarity of the BChl dimer’s protein...     

Suppression of Nucleotide Metabolism Underlies the Establishment and Maintenance of Oncogene-Induced Senescence

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Highlights? Addition of exogenous nucleosides reverses the senescence-associated cell growth arrest ? RRM2 repression drives the decrease in dNTP levels to promote senescence ? RRM2 repression is both necessary and sufficient for senescence ? RRM2 repression correlates with melanocyte senescence status in nevi and melanoma     

Effects of amphibian phylogeny,climate and human impact on the occurrence of the amphibian‐killing chytrid fungus

Chytridiomycosis, due to the fungus Batrachochytrium dendrobatidis (Bd), has been associated with the alarming decline and extinction crisis of amphibians worldwide. Because conservation programs are implemented locally, it is essential to understand how the complex interactions among host species, climate and human activities contribute to Bd occurrence at regional scales. Using weighted phylogenetic regressions and model selection, we investigated geographic patterns of Bd occurrence along a latitudinal gradient of 1500 km within a biodiversity hot spot in Chile (1845 individuals sampled from 253 sites and representing 24 species), and its association with climatic, socio‐demographic and economic variables. Analyses show that Bd prevalence decreases with latitude although it has increased by almost 10% between 2008 and 2013, possibly reflecting an ongoing spread of Bd following the introduction of Xenopus laevis. Occurrence of Bd was higher in regions with high gross domestic product (particularly near developed centers) and with a high variability in rainfall regimes, whereas models including other bioclimatic or geographic variables, including temperature, exhibited substantially lower fit and virtually no support based on Akaike weights. In addition, Bd prevalence exhibited a strong phylogenetic signal, with five species having high numbers of infected individuals and higher prevalence than the average of 13.3% across all species. Taken together, our results highlight that Bd in Chile might still be spreading south, facilitated by a subset of species that seem to play an important epidemiological role maintaining this pathogen in the communities, in combination with climatic and human factors affecting the availability and quality of amphibian breeding sites. This information may be employed to design conservation strategies and mitigate the impacts of Bd in the biodiversity hot spot of southern Chile, and similar studies may prove useful to disentangle the role of different factors contributing to the emergence and spread of this catastrophic disease.     

Amphibian phylogenetic diversity in the face of future climate change: not so good news for the chilean biodiversity hotspot

Biodiversity and Conservation - Climate change is projected to be the most extensive human-induced disturbance to occur on natural ecosystems, inducing changes in different biodiversity features...     

Significance of oxygen carriers and role of liquid paraffin in improving validamycin A production

Validamycin A (Val-A) synthesized by Streptomyces hygroscopicus 5008 is widely used as a high-efficient antibiotic to protect plants from sheath blight disease. A novel fermentation strategy was introduced to stimulate Val-A production by adding oxygen carriers. About 58 % increase in Val-A production was achieved using liquid paraffin. Further, biomass, carbon source, metabolic genes, and metabolic enzymes were studied. It was also found that the supplementation of liquid paraffin increased the medium dissolved oxygen and intracellular oxidative stress level. The expression of the global regulators afsR and soxR sensitive to ROS, ugp catalyzing synthesis of Val-A precursor, and Val-A structural genes was enhanced. The change of the activities of glucose-6-phosphate dehydrogenase and glyceraldehyde 3-phosphate dehydrogenase was observed, which reflected the redirection of carbon metabolic flux. Based on these results, liquid paraffin addition as an oxygen carrier could be a useful technique in industrial production of Val-A and our study revealed a redox-based secondary metabolic regulation in S. hygroscopicus 5008, which provided a new insight into the regulation of the biosynthesis of secondary metabolites.     

Insights into metal ion binding in phospholipases A2: ultra high-resolution crystal structures of an acidic phospholipase A2 in the Ca2+ free and bound states

The electrophile Ca(2+) is an essential multifunctional co-factor in the phospholipase A(2) mediated hydrolysis of phospholipids. Crystal structures of an acidic phospholipase A(2) from the venom of Bothrops jararacussu have been determined both in the Ca(2+) free and bound states at 0.97 and 1.60 A resolutions, respectively. In the Ca(2+) bound state, the Ca(2+) ion is penta-coordinated by a distorted pyramidal cage of oxygen and nitrogen atoms that is significantly different to that observed in structures of other Group I/II phospholipases A(2). In the absence of Ca(2+), a water molecule occupies the position of the Ca(2+) ion and the side chain of Asp49 and the calcium-binding loop adopts a different conformation.     

Why do protein architectures have boltzmann-like statistics?

A theoretical study has shown that the occurrence of various structural elements in stable folds of random copolymers is exponentially dependent on the own energy of the element. A similar occurrence-on-energy dependence is observed in globular proteins¹ from the level of amino acid conformations to the level of overall architectures. Thus, the structural features stabilized by many random sequences are typical of globular proteins while the features rarely observed in proteins are those which are stabilized by only a minor part of the random sequences. © 1995 Wiley-Liss, Inc.     

Perfect temperature for protein structure prediction and folding

We have investigated the influence of the “noise” of inevitable errors in energetic parameters on-protein structure prediction. Because of this noise, only a part of all the interactions operating in a protein chain can be taken into account, and therefore a search for the energy minimum becomes inadequate for protein structure prediction. One can rather rely on statistical mechanics: a calculation carried out at a temperature T_* somewhat below that of protein melting gives the best possible, though always approximate prediction. The early stages of protein folding also “take into account” only a part of all the interactions; consequently, the same temperature T_* is favorable for the self-organization of native-like intermediates in protein folding. © 1995 Wiley-Liss, Inc.     

Asp49 phospholipase A(2)-elaidoylamide complex: a new mode of inhibition

The inhibition of phospholipase A(2)s (PLA(2)s) is of pharmacological and therapeutic interest because these enzymes are involved in several inflammatory diseases. Elaidoylamide is a powerful inhibitor of a neurotoxic PLA(2) from the Vipera ammodytes meridionalis venom. The X-ray structure of the enzyme-inhibitor complex reveals a new mode of Asp49 PLA(2) inhibition by a fatty acid hydrocarbon chain. The structure contains two identical homodimers in the asymmetric unit. In each dimer one subunit is rotated by 180 degrees with respect to the other and the two molecules are oriented head-to-tail. One molecule of elaidoylamide is bound simultaneously to the substrate binding sites of two associated neurotoxic phospholipase A(2) molecules. The inhibitor binds symmetrically to the hydrophobic channels of the two monomers. The structure can be used to design anti-inflammatory drugs.