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61.
Martin González-Andrade Rogelio Rodríguez-Sotres Abraham Madariaga-Mazón José Rivera-Chávez Rachel Mata Alejandro Sosa-Peinado 《Journal of biomolecular structure & dynamics》2016,34(1):78-91
In order to contribute to the structural basis for rational design of calmodulin (CaM) inhibitors, we analyzed the interaction of CaM with 14 classic antagonists and two compounds that do not affect CaM, using docking and molecular dynamics (MD) simulations, and the data were compared to available experimental data. The Ca2+-CaM-Ligands complexes were simulated 20 ns, with CaM starting in the “open” and “closed” conformations. The analysis of the MD simulations provided insight into the conformational changes undergone by CaM during its interaction with these ligands. These simulations were used to predict the binding free energies (ΔG) from contributions ΔH and ΔS, giving useful information about CaM ligand binding thermodynamics. The ΔG predicted for the CaM’s inhibitors correlated well with available experimental data as the r2 obtained was 0.76 and 0.82 for the group of xanthones. Additionally, valuable information is presented here: I) CaM has two preferred ligand binding sites in the open conformation known as site 1 and 4, II) CaM can bind ligands of diverse structural nature, III) the flexibility of CaM is reduced by the union of its ligands, leading to a reduction in the Ca2+-CaM entropy, IV) enthalpy dominates the molecular recognition process in the system Ca2+-CaM-Ligand, and V) the ligands making more extensive contact with the protein have higher affinity for Ca2+-CaM. Despite their limitations, docking and MD simulations in combination with experimental data continue to be excellent tools for research in pharmacology, toward a rational design of new drugs. 相似文献
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Mutations in the human homolog of the Vhlh gene [encoding the von-Hippel Lindau (VHL) protein] lead to tumor development. In mice, depletion of Vhlh in pancreatic ß-cells causes perturbed glucose homeostasis, but the role of this gene in other pancreatic cells is poorly understood. To investigate the function of VHL/HIF pathway in pancreatic cells, we inactivated Vhlh in the pancreatic epithelium as well as in the endocrine and exocrine lineages. Our results show that embryonic depletion of Vhlh within the pancreatic epithelium causes postnatal lethality due to severe hypoglycemia. The hypoglycemia is recapitulated in mice with endocrine-specific removal of Vhlh, while animals with loss of Vhlh predominantly in the exocrine compartment survive to adulthood with no overt defects in glucose metabolism. Mice with hypoglycemia display diminished insulin release in response to elevated glucose. Significantly, the glucagon response is impaired both in vivo (circulating glucagon levels) as well as in an in vitro secretion assay in isolated islets. Hypoxia also impairs glucagon secretion in a glucagon-expressing cell line in culture. Our results reveal a novel role for the hypoxia/HIF pathway in islet hormone secretion and maintenance of the fine balance that allows for the establishment of normoglycemia. 相似文献
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65.
This study focuses on the isolation and characterization of a high cadmium (Cd)-resistant bacterial strain, and possible exploitation
of its Cd-accumulation and Cd-induced siderophore production property to improve plant growth in cadmium-contaminated soil
through root colonization. The bacterial strain could tolerate up to 8 mM of Cd and could accumulate Cd intracellularly. The
strain showed Cd-induced siderophore production maximally at 1.75 mM of Cd concentration under culture condition. It stimulated
the growth of mustard and pumpkin plants in Cd-added soil through its establishment in rhizosphere. Through biochemical characterization
and 16S rDNA sequence analysis, the strain KUCd1, as the name given to it, was identified as a strain of Pseudomonas
aeruginosa. 相似文献
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68.
Martínez MA Delgado OD Breccia JD Baigorí MD Siñeriz F 《Extremophiles : life under extreme conditions》2002,6(5):391-395
Bacillus sp. MIR32 has been isolated using xylan as the only carbon source, and one of its xylanolytic enzymes has been extensively studied. Biochemical analysis first related this strain to Bacillus amyloliquefaciens, but further studies based on a comparison of 16S rDNA sequences, G+C content, and DNA-DNA hybridization showed that strain MIR32 should be classified as a member of the species Bacillus halodurans. This change is also supported by the typical phenotype observed and by the results of PCR amplification directed toward spacers in rDNA and tDNA genes, which were assayed and compared with those of B. halodurans DSM 497(T). Although among alkaliphilic bacilli competence development has not been experimentally demonstrated, in this work both B. halodurans MIR32 and DSM 497(T) were transformed according to a simple procedure developed in our laboratory, reaching 10(2)-10(3) stable transformants per microgram of plasmid DNA. 相似文献
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70.
Alejandro R. Giraudo Silvia D. Matteucci Julián Alonso Justo Herrera Raúl R. Abramson 《Biodiversity and Conservation》2008,17(5):1251-1265
The Atlantic Forest (AF) is one of the five most threatened and megadiverse world hotspots. It is arguably the most devastated
and highly threatened ecosystem on the planet. The vast scope of habitat loss and extreme fragmentation in the AF hotspots
has left intact very few extensive and continuous forested fragments. We compared bird assemblages between small (<100 ha)
and large (>6,000 ha) forest remnants, in one of the largest AF remnants in Argentina. We performed 84 point-counts of birds
in four large fragments (LF) and 67 points in 25 small fragments (SF). We recorded 4,527 bird individuals belonging to 173
species; 2,632 belonging to 153 species in LF and 1,897 in 124 species in SF. Small fragments suffered a significant loss
of bird richness, mainly forest dependent species, but the birds abundance did not decrease, due to an increase in abundance
of forest independent and semi-dependent bird species (edge and non forest species) that benefit from forest fragmentation.
The bird guilds of frugivores, undestory, terrestrial and midstory insectivores, nectarivores and raptors, and the endemic
species of AF were area sensitive, decreasing significantly in richness and abundance in the SF. Terrestrial granivores were
the only guild positively affected by forest fragmentation, containing mainly edge species, which forage in open areas or
borders including crops. Our first observations on fragmentation effects on bird assemblages in the southernmost Argentinean
Atlantic Forests did not validate the hypothesis on pre-adaptation to human disturbances in the bird communities of AF. On
the contrary, we observed that forest dependent, endemic and several sensitive bird guilds were strongly affected by fragmentation,
putting in evidence the vulnerability to the fragmentation process and the necessity to conserve large remnants to avoid reduction
of the high biodiversity of AF birds. 相似文献