PreBI: prediction of biological interfaces of proteins in crystals

PreBI is a server that predicts biological interfaces in protein crystal structures, according to the complementarity and the area of the interface. The server accepts a coordinate file in the PDB format, and all of the possible interfaces are generated automatically, according to the symmetry operations given in the coordinate file. For all of the interfaces generated, the complementarities of the electrostatic potential, hydrophobicity and shape of the interfaces are analyzed, and the most probable biological interface is identified according to the combination of the degree of complementarity derived from the database analyses and the area of the interface. The results can be checked through an interactive viewer, and the most probable complex can be downloaded as atomic coordinates in the PDB format. PreBI is available at

Identification of hepta-histidine as a candidate drug for Huntington's disease by in silico-in vitro- in vivo-integrated screens of chemical libraries.

We identified drug seeds for treating Huntington's disease (HD) by combining in vitro single molecule fluorescence spectroscopy, in silico molecular docking simulations, and in vivo fly and mouse HD models to screen for inhibitors of abnormal interactions between mutant Htt and physiological Ku70, an essential DNA damage repair protein in neurons whose function is known to be impaired by mutant Htt. From 19,468 and 3,010,321 chemicals in actual and virtual libraries, fifty-six chemicals were selected from combined in vitro-in silico screens; six of these were further confirmed to have an in vivo effect on lifespan in a fly HD model, and two chemicals exerted an in vivo effect on the lifespan, body weight and motor function in a mouse HD model. Two oligopeptides, hepta-histidine (7H) and Angiotensin III, rescued the morphological abnormalities of primary neurons differentiated from iPS cells of human HD patients. For these selected drug seeds, we proposed a possible common structure. Unexpectedly, the selected chemicals enhanced rather than inhibited Htt aggregation, as indicated by dynamic light scattering analysis. Taken together, these integrated screens revealed a new pathway for the molecular targeted therapy of HD

JMJ Histone Demethylases Balance H3K27me3 and H3K4me3 Levels at the HSP21 Locus during Heat Acclimation in Arabidopsis

Exposure to moderately high temperature enables plants to acquire thermotolerance to high temperatures that might otherwise be lethal. In Arabidopsis thaliana, histone H3 lysine 27 trimethylation (H3K27me3) at the heat shock protein 17.6C (HSP17.6C) and HSP22 loci is removed by Jumonji C domain-containing protein (JMJ) histone demethylases, thus allowing the plant to ‘remember’ the heat experience. Other heat memory genes, such as HSP21, are downregulated in acclimatized jmj quadruple mutants compared to the wild type, but how those genes are regulated remains uncharacterized. Here, we show that histone H3 lysine 4 trimethylation (H3K4me3) at HSP21 was maintained at high levels for at least three days in response to heat. This heat-dependent H3K4me3 accumulation was compromised in the acclimatized jmj quadruple mutant as compared to the acclimatized wild type. JMJ30 directly bound to the HSP21 locus in response to heat and coordinated H3K27me3 and H3K4me3 levels under standard and fluctuating conditions. Our results suggest that JMJs mediate the balance between H3K27me3 and H3K4me3 at the HSP21 locus through proper maintenance of H3K27me3 removal during heat acclimation

Expression profiling of H3K27me3 demethylase genes during plant development and in response to environmental stress in Arabidopsis

Histone modification influences gene expression. Among histone modifications, H3K27me3 is associated with downregulation of nearby genes via chromatin compaction. In Arabidopsis thaliana, a subset of JUMONJI C DOMAIN-CONTAINING PROTEIN (JMJ) proteins play a critical role in removal of H3K27me3 during plant development or in response to environmental cues. However, the regulation of H3K27me3 demethylase gene expression is not yet fully characterized. In this study, we computationally characterized the expression patterns of JMJ H3K27me3 demethylase genes using public transcriptome datasets created across plant development and after various environmental cues. Consistent with the available transcriptome datasets, GUS staining validated that JMJ30 was highly expressed in the L1 layer of the shoot apical meristem. Furthermore, expression data for panel of five H3K27me3 demethylase genes revealed JMJ30 to be the most highly affected by abiotic and biotic stress. In addition, JMJ30 expression was variable between Arabidopsis thaliana accessions. Finally, the expression of a JMJ30 orthologue from the related species Arabidopsis halleri, AhgJMJ30, fluctuated under field conditions. Taken together, our results suggest that transcriptional changes of H3K27me3 demethylase genes may play key roles in development and environmental responses