The conserved crown bridge loop at the catalytic centre of enzymes of the haloacid dehalogenase superfamily

The crown bridge loop is hexapeptide motif in which the backbone carbonyl group at position 1 is hydrogen bonded to the backbone imino groups of positions 4 and 6. Residues at positions 1 and 4–6 are held in a tight substructure, but different orientations of the plane of the peptide bond between positions 2 and 3 result in two conformers: the 2,3-αRαR crown bridge loop — found in approximately 7% of proteins — and the 2,3-βRαL crown bridge loop, found in approximately 1–2% of proteins. We constructed a relational database in which we identified 60 instances of the 2,3-βRαL conformer, and find that about half occur in enzymes of the haloacid dehalogenase (HAD) superfamily, where they are located next to the catalytic aspartate residue. Analysis of additional enzymes of the HAD superfamily in the extensive SCOPe dataset showed this crown bridge loop to be a conserved feature. Examination of available structures showed that the 2,3-βRαL conformation — but not the 2,3-αRαR conformation — allows the backbone carbonyl group at position 2 to interact with the essential Mg2+ ion. The possibility of interconversion between the 2,3-βRαL and 2,3-αRαR conformations during catalysis is discussed

Identification and characterization of two classes of G1 β-bulge

In standard β-bulges, a residue in one strand of a β-sheet forms hydrogen bonds to two successive residues (`1' and `2') of a second strand. Two categories, `classic' and `G1' β-bulges, are distinguished by their dihedral angles: 1,2-αRβR (classic) or 1,2-αLβR (G1). It had previously been observed that G1 β-bulges are most often found as components of two quite distinct composite structures, suggesting that a basis for further differentiation might exist. Here, it is shown that two subtypes of G1 β-bulges, G1α and G1β, may be distinguished by their conformation (αR or βR) at residue `0' of the second strand. β-Bulges that are constituents of the composite structure named the β-bulge loop are of the G1α type, whereas those that are constituents of the composite structure named β-link here are of the G1β type. A small proportion of G1β β-bulges, but not G1α β-bulges, occur in other contexts. There are distinctive differences in amino-acid composition and sequence pattern between these two types of G1 β-bulge which may have practical application in protein design

BeetleAtlas: an ontogenetic and tissue-specific transcriptomic atlas of the red flour beetle Tribolium castaneum

The red flour beetle Tribolium castaneum has emerged as a powerful model in insect functional genomics. However, a major limitation in the field is the lack of a detailed spatio-temporal view of the genetic signatures underpinning the function of distinct tissues and life stages. Here, we present an ontogenetic and tissue-specific web-based resource for Tribolium transcriptomics: BeetleAtlas (https://www.beetleatlas.org). This web application provides access to a database populated with quantitative expression data for nine adult and seven larval tissues, as well as for four embryonic stages of Tribolium. BeetleAtlas allows one to search for individual Tribolium genes to obtain values of both total gene expression and enrichment in different tissues, together with data for individual isoforms. To facilitate cross-species studies, one can also use Drosophila melanogaster gene identifiers to search for related Tribolium genes. For retrieved genes there are options to identify and display the tissue expression of related Tribolium genes or homologous Drosophila genes. Five additional search modes are available to find genes conforming to any of the following criteria: exhibiting high expression in a particular tissue; showing significant differences in expression between larva and adult; having a peak of expression at a specific stage of embryonic development; belonging to a particular functional category; and displaying a pattern of tissue expression similar to that of a query gene. We illustrate how the different feaures of BeetleAtlas can be used to illuminate our understanding of the genetic mechanisms underpinning the biology of what is the largest animal group on earth

Motivated proteins: a web application for studying small three-dimensional protein motifs

<b>BACKGROUND:</b> Small loop-shaped motifs are common constituents of the three-dimensional structure of proteins. Typically they comprise between three and seven amino acid residues, and are defined by a combination of dihedral angles and hydrogen bonding partners. The most abundant of these are alphabeta-motifs, asx-motifs, asx-turns, beta-bulges, beta-bulge loops, beta-turns, nests, niches, Schellmann loops, ST-motifs, ST-staples and ST-turns.We have constructed a database of such motifs from a range of high-quality protein structures and built a web application as a visual interface to this. <b>DESCRIPTION:</b> The web application, Motivated Proteins, provides access to these 12 motifs (with 48 sub-categories) in a database of over 400 representative proteins. Queries can be made for specific categories or sub-categories of motif, motifs in the vicinity of ligands, motifs which include part of an enzyme active site, overlapping motifs, or motifs which include a particular amino acid sequence. Individual proteins can be specified, or, where appropriate, motifs for all proteins listed. The results of queries are presented in textual form as an (X)HTML table, and may be saved as parsable plain text or XML. Motifs can be viewed and manipulated either individually or in the context of the protein in the Jmol applet structural viewer. Cartoons of the motifs imposed on a linear representation of protein secondary structure are also provided. Summary information for the motifs is available, as are histograms of amino acid distribution, and graphs of dihedral angles at individual positions in the motifs. <b>CONCLUSION:</b> Motivated Proteins is a publicly and freely accessible web application that enables protein scientists to study small three-dimensional motifs without requiring knowledge of either Structured Query Language or the underlying database schem

FlyAtlas 2:a new version of the Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data

FlyAtlas 2 (www.flyatlas2.org) is part successor, part complement to the FlyAtlas database and web application for studying the expression of the genes of Drosophila melanogaster in different tissues of adults and larvae. Although generated in the same lab with the same fly line raised on the same diet as FlyAtlas, the FlyAtlas2 resource employs a completely new set of expression data based on RNA-Seq, rather than microarray analysis, and so it allows the user to obtain information for the expression of different transcripts of a gene. Furthermore, the data for somatic tissues are now available for both male and female adult flies, allowing studies of sexual dimorphism. Gene coverage has been extended by the inclusion of microRNAs and many of the RNA genes included in Release 6 of the Drosophila reference genome. The web interface has been modified to accommodate the extra data, but at the same time has been adapted for viewing on small mobile devices. Users also have access to the RNA-Seq reads displayed alongside the annotated Drosophila genome in the (external) UCSC browser, and are able to link out to the previous FlyAtlas resource to compare the data obtained by RNA-Seq with that obtained using microarrays

A parton picture of de Sitter space during slow-roll inflation

It is well-known that expectation values in de Sitter space are afflicted by infra-red divergences. Long ago, Starobinsky proposed that infra-red effects in de Sitter space could be accommodated by evolving the long-wavelength part of the field according to the classical field equations plus a stochastic source term. I argue that--when quantum-mechanical loop corrections are taken into account--the separate-universe picture of superhorizon evolution in de Sitter space is equivalent, in a certain leading-logarithm approximation, to Starobinsky's stochastic approach. In particular, the time evolution of a box of de Sitter space can be understood in exact analogy with the DGLAP evolution of partons within a hadron, which describes a slow logarithmic evolution in the distribution of the hadron's constituent partons with the energy scale at which they are probed.Comment: 36 pages; uses iopart.cls and feynmp.sty. v2: Minor typos corrected. Matches version published in JCA