Protein Data Bank In Europe Research Articles

An update on the Enzyme Portal: an integrative approach for exploring enzyme knowledge.

Enzymes are a key part of life processes and are increasingly important for various areas of research such as medicine, biotechnology, bioprocessing and drug research. The goal of the Enzyme Portal is to provide an interface to all European Bioinformatics Institute (EMBL-EBI) data about enzymes (de Matos, P., et al., (2013), BMC Bioinformatics, 14 (1), 103). These data include enzyme function, sequence features and family classification, protein structure, reactions, pathways, small molecules, diseases and the associated literature. The sources of enzyme data are: the UniProt Knowledgebase (UniProtKB) (UniProt Consortium, 2015), the Protein Data Bank in Europe (PDBe), (Valenkar, S., et al., Nucleic Acids Res.2016; 44, D385–D395) Rhea—a database of enzyme-catalysed reactions (Morgat, A., et al., Nucleic Acids Res. 2015; 43, D459-D464), Reactome—a database of biochemical pathways (Fabregat, A., et al., Nucleic Acids Res. 2016; 44, D481–D487), IntEnz—a resource with enzyme nomenclature information (Fleischmann, A., et al., Nucleic Acids Res. 2004 32, D434–D437) and ChEBI (Hastings, J., et al., Nucleic Acids Res. 2013) and ChEMBL (Bento, A. P., et al., Nucleic Acids Res. 201442, 1083–1090)—resources which contain information about small-molecule chemistry and bioactivity. This article describes the redesign of Enzyme Portal and the increased functionality added to maximise integration and interpretation of these data. Use case examples of the Enzyme Portal and the versatile workflows its supports are illustrated. We welcome the suggestion of new resources for integration.

Protein Data Bank (PDB): The Single Global Macromolecular Structure Archive.

The Protein Data Bank (PDB)--the single global repository of experimentally determined 3D structures of biological macromolecules and their complexes--was established in 1971, becoming the first open-access digital resource in the biological sciences. The PDB archive currently houses ~130,000 entries (May 2017). It is managed by the Worldwide Protein Data Bank organization (wwPDB; wwpdb.org), which includes the RCSB Protein Data Bank (RCSB PDB; rcsb.org), the Protein Data Bank Japan (PDBj; pdbj.org), the Protein Data Bank in Europe (PDBe; pdbe.org), and BioMagResBank (BMRB; www.bmrb.wisc.edu). The four wwPDB partners operate a unified global software system that enforces community-agreed data standards and supports data Deposition, Biocuration, and Validation of ~11,000 new PDB entries annually (deposit.wwpdb.org). The RCSB PDB currently acts as the archive keeper, ensuring disaster recovery of PDB data and coordinating weekly updates. wwPDB partners disseminate the same archival data from multiple FTP sites, while operating complementary websites that provide their own views of PDB data with selected value-added information and links to related data resources. At present, the PDB archives experimental data, associated metadata, and 3D-atomic level structural models derived from three well-established methods: crystallography, nuclear magnetic resonance spectroscopy (NMR), and electron microscopy (3DEM). wwPDB partners are working closely with experts in related experimental areas (small-angle scattering, chemical cross-linking/mass spectrometry, Forster energy resonance transfer or FRET, etc.) to establish a federation of data resources that will support sustainable archiving and validation of 3D structural models and experimental data derived from integrative or hybrid methods.

PDBe: improved accessibility of macromolecular structure data from PDB and EMDB.

The Protein Data Bank in Europe (http://pdbe.org) accepts and annotates depositions of macromolecular structure data in the PDB and EMDB archives and enriches, integrates and disseminates structural information in a variety of ways. The PDBe website has been redesigned based on an analysis of user requirements, and now offers intuitive access to improved and value-added macromolecular structure information. Unique value-added information includes lists of reviews and research articles that cite or mention PDB entries as well as access to figures and legends from full-text open-access publications that describe PDB entries. A powerful new query system not only shows all the PDB entries that match a given query, but also shows the ‘best structures’ for a given macromolecule, ligand complex or sequence family using data-quality information from the wwPDB validation reports. A PDBe RESTful API has been developed to provide unified access to macromolecular structure data available in the PDB and EMDB archives as well as value-added annotations, e.g. regarding structure quality and up-to-date cross-reference information from the SIFTS resource. Taken together, these new developments facilitate unified access to macromolecular structure data in an intuitive way for non-expert users and support expert users in analysing macromolecular structure data.

New wwPDB validation pipelines for X-ray, NMR and 3DEM structures

The Protein Data Bank (PDB) is the single global archive of 3D biomacromolecular structure data. The archive is managed by the Worldwide Protein Data Bank (wwPDB; wwpdb.org) organisation through its partners, the Research Collaboratory for Structural Bioinformatics (RCSB PDB), the Protein Data Bank Japan (PDBj), the Protein Data Bank in Europe and the Biological Magnetic Resonance Bank (BMRB). Analogously, the Electron Microscopy Data Bank (EMDB) is managed by the EMDataBank (emdatabank.org) organisation. A few years ago, realising the needs and opportunities to assess the quality of biomacromolecular structures deposited in the PDB, the wwPDB and EMDataBank partners established Validation Task Forces (VTFs) to advice them on up-to-date and community-agreed methods and standards to validate X-ray, NMR and 3DEM structures and data. All three VTFs have now published their recommendations (1, 2, 3) and these are getting implemented as validation-software pipelines . The pipelines are integrated in the new joint wwPDB deposition and annotation system (http://deposit.wwpdb.org/deposition/). In addition, stand-alone servers are provided to allow practising structural biologists to validate models prior to publication and deposition (http://wwpdb.org/validation-servers.html). The validation pipelines and the output they produce (human-readable PDF reports and machine-readable XML files) will be described.

Educational Outreach and User Training at the Worldwide Protein Data Bank

The Protein Data Bank (PDB) contains a wealth of structural and functional knowledge about proteins, RNA, DNA, and other macromolecules, and their assemblies and complexes with small molecules. The challenge faced by the providers of PDB data is to make this knowledge accessible to an increasingly large and diverse audience, ranging from expert structural biologists to non-specialist consumers of structural information. Educators, students, and general audiences will have their own specific interests and expectations from molecular structure data. For a general user, a 2D image of hemoglobin illustrates how a protein looks at a microscopic level. For high school students and educators, 3D models or computer graphics can show how one or a few specific proteins can assemble into an icosahedral virus. In contrast, PhD and post-doc level researchers require expert guidance on how to critically assess the quality of structural data, and in-depth training on the use of specialist tools and resources for the comparison and analysis of structures. The PDB archive is managed by members of the Worldwide Protein Data Bank (wwPDB): the Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB; rcsb.org), Protein Data Bank in Europe (PDBe; pdbe.org), Protein Data Bank Japan (PDBj), and BioMagResBank (BMRB, bmrb.wisc.edu). In addition to managing and distributing structural data, the wwPDB partners are engaged in numerous outreach initiatives and user training programs. These efforts are vital to ensuring that these uniquely valuable data can be effectively accessed and used by research scientists, students, and educators alike. This talk will describe on-going wwPDB outreach efforts and highlight exciting new initiatives at the RCSB PDB, PDBe and PDBj.

Structure of the monofunctional heme catalase DR1998 from Deinococcusradiodurans.

Deinococcus radiodurans is an aerobic organism with the ability to survive under conditions of high radiation doses or desiccation. As part of its protection system against oxidative stress, this bacterium encodes three monofunctional catalases. The DR1998 catalase belongs to clade 1, and is present at high levels under normal growth conditions. The crystals of DR1998 diffracted very weakly, and the merged diffraction data showed an R sym of 0.308. Its crystal structure was determined and refined to 2.6 Å. The four molecules present in the asymmetric unit form, by crystallographic symmetry, two homotetramers with 222 point-group symmetry. The overall structure of DR1998 is similar to that of other monofunctional catalases, showing higher structural homology with the catalase structures of clade 1. Each monomer shows the typical catalase fold, and contains one heme b in the active site. The heme is coordinated by the proximal ligand Tyr369, and on the heme distal side the essential His81 and Asn159 are hydrogen-bonded to a water molecule. A 25-Å-long channel is the main channel connecting the active site to the external surface. This channel starts with a hydrophobic region from the catalytic heme site, which is followed by a hydrophilic region that begins on Asp139 and expands up to the protein surface. Apart from this channel, an alternative channel, also near the heme active site, is presented and discussed. Coordinates and structure factors have been deposited in the Protein Data Bank in Europe under accession code 4CAB.

PDBe: Protein Data Bank in Europe

The Protein Data Bank in Europe (pdbe.org) is a founding member of the Worldwide PDB consortium (wwPDB; wwpdb.org) and as such is actively engaged in the deposition, annotation, remediation and dissemination of macromolecular structure data through the single global archive for such data, the PDB. Similarly, PDBe is a member of the EMDataBank organisation (emdatabank.org), which manages the EMDB archive for electron microscopy data. PDBe also develops tools that help the biomedical science community to make effective use of the data in the PDB and EMDB for their research. Here we describe new or improved services, including updated SIFTS mappings to other bioinformatics resources, a new browser for the PDB archive based on Gene Ontology (GO) annotation, updates to the analysis of Nuclear Magnetic Resonance-derived structures, redesigned search and browse interfaces, and new or updated visualisation and validation tools for EMDB entries.

Web-based visualisation and analysis of 3D electron-microscopy data from EMDB and PDB.

The Protein Data Bank in Europe (PDBe) has developed web-based tools for the visualisation and analysis of 3D electron microscopy (3DEM) structures in the Electron Microscopy Data Bank (EMDB) and Protein Data Bank (PDB). The tools include: (1) a volume viewer for 3D visualisation of maps, tomograms and models, (2) a slice viewer for inspecting 2D slices of tomographic reconstructions, and (3) visual analysis pages to facilitate analysis and validation of maps, tomograms and models. These tools were designed to help non-experts and experts alike to get some insight into the content and assess the quality of 3DEM structures in EMDB and PDB without the need to install specialised software or to download large amounts of data from these archives. The technical challenges encountered in developing these tools, as well as the more general considerations when making archived data available to the user community through a web interface, are discussed.

SIFTS: Structure Integration with Function, Taxonomy and Sequences resource

The Structure Integration with Function, Taxonomy and Sequences resource (SIFTS; http://pdbe.org/sifts) is a close collaboration between the Protein Data Bank in Europe (PDBe) and UniProt. The two teams have developed a semi-automated process for maintaining up-to-date cross-reference information to UniProt entries, for all protein chains in the PDB entries present in the UniProt database. This process is carried out for every weekly PDB release and the information is stored in the SIFTS database. The SIFTS process includes cross-references to other biological resources such as Pfam, SCOP, CATH, GO, InterPro and the NCBI taxonomy database. The information is exported in XML format, one file for each PDB entry, and is made available by FTP. Many bioinformatics resources use SIFTS data to obtain cross-references between the PDB and other biological databases so as to provide their users with up-to-date information.

PDBe: Protein Data Bank in Europe

The Protein Data Bank in Europe (PDBe; pdbe.org) is a partner in the Worldwide PDB organization (wwPDB; wwpdb.org) and as such actively involved in managing the single global archive of biomacromolecular structure data, the PDB. In addition, PDBe develops tools, services and resources to make structure-related data more accessible to the biomedical community. Here we describe recently developed, extended or improved services, including an animated structure-presentation widget (PDBportfolio), a widget to graphically display the coverage of any UniProt sequence in the PDB (UniPDB), chemistry- and taxonomy-based PDB-archive browsers (PDBeXplore), and a tool for interactive visualization of NMR structures, corresponding experimental data as well as validation and analysis results (Vivaldi).

The Protein Data Bank in Europe (PDBe): bringing structure to biology

The Protein Data Bank in Europe (PDBe) is the European partner in the Worldwide PDB and as such handles depositions of X-ray, NMR and EM data and structure models. PDBe also provides advanced bioinformatics services based on data from the PDB and related resources. Some of the challenges facing the PDB and its guardians are discussed, as well as some of the areas on which PDBe activities will focus in the future (advanced services, ligands, integration, validation and experimental data). Finally, some recent developments at PDBe are described.

Protein structure reports in JIMD ‐ an important enhancement of journal scope

Protein structure reports in JIMD ‐ an important enhancement of journal scope

The 2011 Nucleic Acids Research Database Issue and the online Molecular Biology Database Collection

The current 18th Database Issue of Nucleic Acids Research features descriptions of 96 new and 83 updated online databases covering various areas of molecular biology. It includes two editorials, one that discusses COMBREX, a new exciting project aimed at figuring out the functions of the ‘conserved hypothetical’ proteins, and one concerning BioDBcore, a proposed description of the ‘minimal information about a biological database’. Papers from the members of the International Nucleotide Sequence Database collaboration (INSDC) describe each of the participating databases, DDBJ, ENA and GenBank, principles of data exchange within the collaboration, and the recently established Sequence Read Archive. A testament to the longevity of databases, this issue includes updates on the RNA modification database, Definition of Secondary Structure of Proteins (DSSP) and Homology-derived Secondary Structure of Proteins (HSSP) databases, which have not been featured here in >12 years. There is also a block of papers describing recent progress in protein structure databases, such as Protein DataBank (PDB), PDB in Europe (PDBe), CATH, SUPERFAMILY and others, as well as databases on protein structure modeling, protein–protein interactions and the organization of inter-protein contact sites. Other highlights include updates of the popular gene expression databases, GEO and ArrayExpress, several cancer gene databases and a detailed description of the UK PubMed Central project. The Nucleic Acids Research online Database Collection, available at: http://www.oxfordjournals.org/nar/database/a/, now lists 1330 carefully selected molecular biology databases. The full content of the Database Issue is freely available online at the Nucleic Acids Research web site (http://nar.oxfordjournals.org/).

PDBe: Protein Data Bank in Europe

The Protein Data Bank in Europe (PDBe; pdbe.org) is actively involved in managing the international archive of biomacromolecular structure data as one of the partners in the Worldwide Protein Data Bank (wwPDB; wwpdb.org). PDBe also develops new tools to make structural data more widely and more easily available to the biomedical community. PDBe has developed a browser to access and analyze the structural archive using classification systems that are familiar to chemists and biologists. The PDBe web pages that describe individual PDB entries have been enhanced through the introduction of plain-English summary pages and iconic representations of the contents of an entry (PDBprints). In addition, the information available for structures determined by means of NMR spectroscopy has been expanded. Finally, the entire web site has been redesigned to make it substantially easier to use for expert and novice users alike. PDBe works closely with other teams at the European Bioinformatics Institute (EBI) and in the international scientific community to develop new resources with value-added information. The SIFTS initiative is an example of such a collaboration—it provides extensive mapping data between proteins whose structures are available from the PDB and a host of other biomedical databases. SIFTS is widely used by major bioinformatics resources.

EMDataBank.org: unified data resource for CryoEM

Cryo-electron microscopy reconstruction methods are uniquely able to reveal structures of many important macromolecules and macromolecular complexes. EMDataBank.org, a joint effort of the Protein Data Bank in Europe (PDBe), the Research Collaboratory for Structural Bioinformatics (RCSB) and the National Center for Macromolecular Imaging (NCMI), is a global ‘one-stop shop’ resource for deposition and retrieval of cryoEM maps, models and associated metadata. The resource unifies public access to the two major archives containing EM-based structural data: EM Data Bank (EMDB) and Protein Data Bank (PDB), and facilitates use of EM structural data of macromolecules and macromolecular complexes by the wider scientific community.

Collaboration, competition, validation and plans for the future

Gerard Kleywegt obtained his PhD in 1991 from the University of Utrecht. After a brief spell with a software company he joined Alwyn Jones’s protein crystallography laboratory in Uppsala. He stayed there for 17 years and developed many tools that are widely used by structural biologists worldwide. From 1996 to 2009 Gerard was involved in running the Swedish Structural Biology Network (SBNet), first as network coordinator and later as program director. From 2002 to 2007 he was a Research Fellow of the Royal Swedish Academy of Sciences. In 2009, he was appointed Professor of Structural Molecular Biology at Uppsala University. Since July 2009 Gerard has been head of the Protein Data Bank in Europe (PDBe) [1, 2] at the European Bioinformatics Institute (EBI) near Cambridge in the United Kingdom. He has an extensive publication record and has served on the PDBe Scientific Advisory Board for some years. He has also been one of the European representatives on the Worldwide PDB (wwPDB) [3] advisory committee.

Peroxisomal Plant 3-Ketoacyl-CoA Thiolase Structure and Activity Are Regulated by a Sensitive Redox Switch

The breakdown of fatty acids, performed by the beta-oxidation cycle, is crucial for plant germination and sustainability. beta-Oxidation involves four enzymatic reactions. The final step, in which a two-carbon unit is cleaved from the fatty acid, is performed by a 3-ketoacyl-CoA thiolase (KAT). The shortened fatty acid may then pass through the cycle again (until reaching acetoacetyl-CoA) or be directed to a different cellular function. Crystal structures of KAT from Arabidopsis thaliana and Helianthus annuus have been solved to 1.5 and 1.8 A resolution, respectively. Their dimeric structures are very similar and exhibit a typical thiolase-like fold; dimer formation and active site conformation appear in an open, active, reduced state. Using an interdisciplinary approach, we confirmed the potential of plant KATs to be regulated by the redox environment in the peroxisome within a physiological range. In addition, co-immunoprecipitation studies suggest an interaction between KAT and the multifunctional protein that is responsible for the preceding two steps in beta-oxidation, which would allow a route for substrate channeling. We suggest a model for this complex based on the bacterial system.

Integration of chemical information with protein sequences and 3D structures

The Protein Data Bank (PDB) contains a wealth of small molecule - macro molecule complexes the study of which contribute enormously to our understanding of the interactions. However, exploiting and mining this treasure trove of data requires advanced analysis and retrieval methods that take into account both types of molecules. One such method is PDBeMotif, that has been developed by the Protein Data Bank in Europe (PDBe) at EMBL-EBI. Utilizing a relational database model at the back-end, the data structure represents a network of molecule, residue and motif interactions as well as their relative positions in the sequence and in 3D. The loader applies a number of algorithms to analyse PDB and derive necessary information, such as planarity and aromaticity of the chemical compounds, hydrogen-bonds network, coordination geometry, bond types (including pi electron interactions), 3D structural motifs, sequence domains and families. It collects information about sequence features, motifs and catalytic sites from available Distributed Annotation System (DAS) resources. The web application allows for a wide variety of searches and data analysis including protein motifs with chemical fragments association, protein sites characterisation, correlating properties, hits multiple sequence and 3D alignments. The whole system is released under GPL and available with the source code from http://sourceforge.net/projects/pdbsam and on line at http://www.ebi.ac.uk/pdbe-site/PDBeMotif/

PDBe: Protein Data Bank in Europe

The Protein Data Bank in Europe (PDBe) (http://www.ebi.ac.uk/pdbe/) is actively working with its Worldwide Protein Data Bank partners to enhance the quality and consistency of the international archive of bio-macromolecular structure data, the Protein Data Bank (PDB). PDBe also works closely with its collaborators at the European Bioinformatics Institute and the scientific community around the world to enhance its databases and services by adding curated and actively maintained derived data to the existing structural data in the PDB. We have developed a new database infrastructure based on the remediated PDB archive data and a specially designed database for storing information on interactions between proteins and bound molecules. The group has developed new services that allow users to carry out simple textual queries or more complex 3D structure-based queries. The newly designed ‘PDBeView Atlas pages’ provide an overview of an individual PDB entry in a user-friendly layout and serve as a starting point to further explore the information available in the PDBe database. PDBe’s active involvement with the X-ray crystallography, Nuclear Magnetic Resonance spectroscopy and cryo-Electron Microscopy communities have resulted in improved tools for structure deposition and analysis.