Update on activities at the Universal Protein Resource (UniProt) in 2013.

The mission of the Universal Protein Resource (UniProt) (http://www.uniprot.org) is to support biological research by providing a freely accessible, stable, comprehensive, fully classified, richly and accurately annotated protein sequence knowledgebase. It integrates, interprets and standardizes data from numerous resources to achieve the most comprehensive catalogue of protein sequences and functional annotation. UniProt comprises four major components, each optimized for different uses, the UniProt Archive, the UniProt Knowledgebase, the UniProt Reference Clusters and the UniProt Metagenomic and Environmental Sequence Database. UniProt is produced by the UniProt Consortium, which consists of groups from the European Bioinformatics Institute (EBI), the SIB Swiss Institute of Bioinformatics (SIB) and the Protein Information Resource (PIR). UniProt is updated and distributed every 4 weeks and can be accessed online for searches or downloads

Investigating the role of loop c hydrophilic residue 'T244' in the binding site of ρ1 GABAC receptors via site mutation and partial agonism

The loop C hydrophilic residue, threonine 244 lines the orthosteric binding site of ρ1 GABAC receptors was studied by point mutation into serine, alanine and cysteine, and tested with GABA, some representative partial agonists and antagonists. Thr244 has a hydroxyl group essential for GABA activity that is constrained by the threonine methyl group, orienting it toward the binding site. Significant decreases in activation effects of the studied ligands at ρ1 T244S mutant receptors, suggests a critical role for this residue. Results of aliphatic and heteroaromatic partial agonists demonstrate different pharmacological effects at ρ1 T244S mutant receptors when co-applied with GABA EC50 responses. ρ1 T244A and ρ1 T244C mutant receptors have minimal sensitivity to GABA at high mM concentrations, whereas, the ρ1 WT partial agonists, β-alanine and MTSEA demonstrate more efficacy and potency, respectively, than GABA at these mutant receptors. This study explores the role of Thr244 in the binding of agonists as an initial step during channel gating by moving loop C towards the ligand

Amino acid metabolism conflicts with protein diversity

The twenty protein coding amino acids are found in proteomes with different relative abundances. The most abundant amino acid, leucine, is nearly an order of magnitude more prevalent than the least abundant amino acid, cysteine. Amino acid metabolic costs differ similarly, constraining their incorporation into proteins. On the other hand, sequence diversity is necessary for protein folding, function and evolution. Here we present a simple model for a cost-diversity trade-off postulating that natural proteomes minimize amino acid metabolic flux while maximizing sequence entropy. The model explains the relative abundances of amino acids across a diverse set of proteomes. We found that the data is remarkably well explained when the cost function accounts for amino acid chemical decay. More than one hundred proteomes reach comparable solutions to the trade-off by different combinations of cost and diversity. Quantifying the interplay between proteome size and entropy shows that proteomes can get optimally large and diverse

Metagenomic analysis of the saliva microbiome with merlin

In recent years, metagenomics has demonstrated to play an essential role on the study of the microorganisms that live in microbial communities, particularly those who inhabit the human body. Several bioinformatics tools and pipelines have been developed for the analysis of these data, but they usually only address one topic: to identify the taxonomic composition or to address the metabolic functional profile. This work aimed to implement a computational framework able to answer the two questions simultaneously. Merlin, a previously released software aiming at the reconstruction of genome-scale metabolic models for single organisms, was extended to deal with metagenomics data. It has an user-friendly and intuitive interface, being suitable for those with limited bioinformatics skills. The performance of the tool was evaluated with samples from the Human Microbiome Project, particularly from saliva. Overall, the results show the same patterns reported before: while the pathways needed for microbial life remain relatively stable, the community composition varies extensively among individuals

The Catalytic Site Atlas 2.0: cataloging catalytic sites and residues identified in enzymes.

Understanding which are the catalytic residues in an enzyme and what function they perform is crucial to many biology studies, particularly those leading to new therapeutics and enzyme design. The original version of the Catalytic Site Atlas (CSA) (http://www.ebi.ac.uk/thornton-srv/databases/CSA) published in 2004, which catalogs the residues involved in enzyme catalysis in experimentally determined protein structures, had only 177 curated entries and employed a simplistic approach to expanding these annotations to homologous enzyme structures. Here we present a new version of the CSA (CSA 2.0), which greatly expands the number of both curated (968) and automatically annotated catalytic sites in enzyme structures, utilizing a new method for annotation transfer. The curated entries are used, along with the variation in residue type from the sequence comparison, to generate 3D templates of the catalytic sites, which in turn can be used to find catalytic sites in new structures. To ease the transfer of CSA annotations to other resources a new ontology has been developed: the Enzyme Mechanism Ontology, which has permitted the transfer of annotations to Mechanism, Annotation and Classification in Enzymes (MACiE) and UniProt Knowledge Base (UniProtKB) resources. The CSA database schema has been re-designed and both the CSA data and search capabilities are presented in a new modern web interface

The genome and transcriptome of Trichormus sp NMC-1: insights into adaptation to extreme environments on the Qinghai-Tibet Plateau

The Qinghai-Tibet Plateau (QTP) has the highest biodiversity for an extreme environment worldwide, and provides an ideal natural laboratory to study adaptive evolution. In this study, we generated a draft genome sequence of cyanobacteria Trichormus sp. NMC-1 in the QTP and performed whole transcriptome sequencing under low temperature to investigate the genetic mechanism by which T. sp. NMC-1 adapted to the specific environment. Its genome sequence was 5.9 Mb with a G+C content of 39.2% and encompassed a total of 5362 CDS. A phylogenomic tree indicated that this strain belongs to the Trichormus and Anabaena cluster. Genome comparison between T. sp. NMC-1 and six relatives showed that functionally unknown genes occupied a much higher proportion (28.12%) of the T. sp. NMC-1 genome. In addition, functions of specific, significant positively selected, expanded orthogroups, and differentially expressed genes involved in signal transduction, cell wall/membrane biogenesis, secondary metabolite biosynthesis, and energy production and conversion were analyzed to elucidate specific adaptation traits. Further analyses showed that the CheY-like genes, extracellular polysaccharide and mycosporine-like amino acids might play major roles in adaptation to harsh environments. Our findings indicate that sophisticated genetic mechanisms are involved in cyanobacterial adaptation to the extreme environment of the QTP

NOVEL IN SILICO APPROACH OF ANTICANCER ACTIVITY BY INHIBITING HEMOPEXIN PROTEINS WITH INDIGOFERA ASPALATHOIDESPLANT CONSTITUENTS AT ACTIVE SITE

Objective: The aim of the study was to investigate the anti-cancer activity using the phytoconstituents of Indigofera aspalathoides.Methods: The plant extract has been largely used as cell proliferation inhibitors. In this study, specific phytoconstituent has been targeted towardsmatrix metalloproteinases (MMPs).Results: MMPs are group of proteinases that are associated with cell invasion inhibition and also inhibit proliferation. The C-terminal domain ofMMPs mimics the serum protein hemopexin (HPX). According to various literatures, a reason for the failure of MMP as anti-cancer agent is thepresence of this HPX binding at the active site.Conclusion: A novel approach was carried to inhibit this binding by Carotal, (-)-Spathulenol, Tau.-Cadinol proteins from the plant I. aspalathoides. Keywords: Hemopexin, Matrix metalloproteinase, Indigofera aspalathoides, Molecular docking, Carotal, (-)-Spathulenol, Tau.-Cadinol

Comparative genome analysis of Wolbachia strain wAu

BACKGROUND: Wolbachia intracellular bacteria can manipulate the reproduction of their arthropod hosts, including inducing sterility between populations known as cytoplasmic incompatibility (CI). Certain strains have been identified that are unable to induce or rescue CI, including wAu from Drosophila. Genome sequencing and comparison with CI-inducing related strain wMel was undertaken in order to better understand the molecular basis of the phenotype. RESULTS: Although the genomes were broadly similar, several rearrangements were identified, particularly in the prophage regions. Many orthologous genes contained single nucleotide polymorphisms (SNPs) between the two strains, but a subset containing major differences that would likely cause inactivation in wAu were identified, including the absence of the wMel ortholog of a gene recently identified as a CI candidate in a proteomic study. The comparative analyses also focused on a family of transcriptional regulator genes implicated in CI in previous work, and revealed numerous differences between the strains, including those that would have major effects on predicted function. CONCLUSIONS: The study provides support for existing candidates and novel genes that may be involved in CI, and provides a basis for further functional studies to examine the molecular basis of the phenotype

cisPath: an R/Bioconductor package for cloud users for visualization and management of functional protein interaction networks

Background: With the burgeoning development of cloud technology and services, there are an increasing number of users who prefer cloud to run their applications. All software and associated data are hosted on the cloud, allowing users to access them via a web browser from any computer, anywhere. This paper presents cisPath, an R/Bioconductor package deployed on cloud servers for client users to visualize, manage, and share functional protein interaction networks. Results: With this R package, users can easily integrate downloaded protein-protein interaction information from different online databases with private data to construct new and personalized interaction networks. Additional functions allow users to generate specific networks based on private databases. Since the results produced with the use of this package are in the form of web pages, cloud users can easily view and edit the network graphs via the browser, using a mouse or touch screen, without the need to download them to a local computer. This package can also be installed and run on a local desktop computer. Depending on user preference, results can be publicized or shared by uploading to a web server or cloud driver, allowing other users to directly access results via a web browser. Conclusions: This package can be installed and run on a variety of platforms. Since all network views are shown in web pages, such package is particularly useful for cloud users. The easy installation and operation is an attractive quality for R beginners and users with no previous experience with cloud services.SCI(E)CPCI-S(ISTP)[email protected]

Improved pan-specific MHC class I peptide binding predictions using a novel representation of the MHC binding cleft environment

Major histocompatibility complex (MHC) molecules play a key role in cell-mediated immune responses presenting bounded peptides for recognition by the immune system cells. Several in silico methods have been developed to predict the binding affinity of a given peptide to a specific MHC molecule. One of the current state-of-the-art methods for MHC class I is NetMHCpan, which has a core ingredient for the representation of the MHC class I molecule using a pseudo-sequence representation of the binding cleft amino acid environment. New and large MHC–peptide-binding data sets are constantly being made available, and also new structures of MHC class I molecules with a bound peptide have been published. In order to test if the NetMHCpan method can be improved by integrating this novel information, we created new pseudo-sequence definitions for the MHC-binding cleft environment from sequence and structural analyses of different MHC data sets including human leukocyte antigen (HLA), non-human primates (chimpanzee, macaque and gorilla) and other animal alleles (cattle, mouse and swine). From these constructs, we showed that by focusing on MHC sequence positions found to be polymorphic across the MHC molecules used to train the method, the NetMHCpan method achieved a significant increase in the predictive performance, in particular, of non-human MHCs. This study hence showed that an improved performance of MHC-binding methods can be achieved not only by the accumulation of more MHC–peptide-binding data but also by a refined definition of the MHC-binding environment including information from non-human species.Fil: Carrasco Pro, Sebastián. Universidad Peruana Cayetano Heredia; PerúFil: Zimic, Mirko. Universidad Peruana Cayetano Heredia; PerúFil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentin