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      The MEROPS database of proteolytic enzymes, their substrates and inhibitors in 2017 and a comparison with peptidases in the PANTHER database

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          Abstract

          The MEROPS database ( http://www.ebi.ac.uk/merops/) is an integrated source of information about peptidases, their substrates and inhibitors. The hierarchical classification is: protein-species, family, clan, with an identifier at each level. The MEROPS website moved to the EMBL-EBI in 2017, requiring refactoring of the code-base and services provided. The interface to sequence searching has changed and the MEROPS protein sequence libraries can be searched at the EMBL-EBI with HMMER, FastA and BLASTP. Cross-references have been established between MEROPS and the PANTHER database at both the family and protein-species level, which will help to improve curation and coverage between the resources. Because of the increasing size of the MEROPS sequence collection, in future only sequences of characterized proteins, and from completely sequenced genomes of organisms of evolutionary, medical or commercial significance will be added. As an example, peptidase homologues in four proteomes from the Asgard superphylum of Archaea have been identified and compared to other archaean, bacterial and eukaryote proteomes. This has given insights into the origins and evolution of peptidase families, including an expansion in the number of proteasome components in Asgard archaeotes and as organisms increase in complexity. Novel structures for proteasome complexes in archaea are postulated.

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          Most cited references18

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          HMMER web server: 2015 update

          The HMMER website, available at http://www.ebi.ac.uk/Tools/hmmer/, provides access to the protein homology search algorithms found in the HMMER software suite. Since the first release of the website in 2011, the search repertoire has been expanded to include the iterative search algorithm, jackhmmer. The continued growth of the target sequence databases means that traditional tabular representations of significant sequence hits can be overwhelming to the user. Consequently, additional ways of presenting homology search results have been developed, allowing them to be summarised according to taxonomic distribution or domain architecture. The taxonomy and domain architecture representations can be used in combination to filter the results according to the needs of a user. Searches can also be restricted prior to submission using a new taxonomic filter, which not only ensures that the results are specific to the requested taxonomic group, but also improves search performance. The repertoire of profile hidden Markov model libraries, which are used for annotation of query sequences with protein families and domains, has been expanded to include the libraries from CATH-Gene3D, PIRSF, Superfamily and TIGRFAMs. Finally, we discuss the relocation of the HMMER webserver to the European Bioinformatics Institute and the potential impact that this will have.
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            PDBsum: Structural summaries of PDB entries

            Abstract PDBsum is a web server providing structural information on the entries in the Protein Data Bank (PDB). The analyses are primarily image‐based and include protein secondary structure, protein‐ligand and protein‐DNA interactions, PROCHECK analyses of structural quality, and many others. The 3D structures can be viewed interactively in RasMol, PyMOL, and a JavaScript viewer called 3Dmol.js. Users can upload their own PDB files and obtain a set of password‐protected PDBsum analyses for each. The server is freely accessible to all at: http://www.ebi.ac.uk/pdbsum.
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              Structure of 20S proteasome from yeast at 2.4 A resolution.

              The crystal structure of the 20S proteasome from the yeast Saccharomyces cerevisiae shows that its 28 protein subunits are arranged as an (alpha1...alpha7, beta1...beta7)2 complex in four stacked rings and occupy unique locations. The interior of the particle, which harbours the active sites, is only accessible by some very narrow side entrances. The beta-type subunits are synthesized as proproteins before being proteolytically processed for assembly into the particle. The proforms of three of the seven different beta-type subunits, beta1/PRE3, beta2/PUP1 and beta5/PRE2, are cleaved between the threonine at position 1 and the last glycine of the pro-sequence, with release of the active-site residue Thr 1. These three beta-type subunits have inhibitor-binding sites, indicating that PRE2 has a chymotrypsin-like and a trypsin-like activity and that PRE3 has peptidylglutamyl peptide hydrolytic specificity. Other beta-type subunits are processed to an intermediate form, indicating that an additional nonspecific endopeptidase activity may exist which is important for peptide hydrolysis and for the generation of ligands for class I molecules of the major histocompatibility complex.
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                Author and article information

                Journal
                Nucleic Acids Res
                Nucleic Acids Res
                nar
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                04 January 2018
                14 November 2017
                14 November 2017
                : 46
                : Database issue , Database issue
                : D624-D632
                Affiliations
                EMBL European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK
                Division of Bioinformatics, Department of Preventive Medicine, University of Southern California, 1450 Biggy St, NRT 2502, Los Angeles, CA 90033, USA
                Author notes
                To whom correspondence should be addressed. Tel: +44 1223 494525; Fax: +44 1223 494468; Email: ndr@ 123456ebi.ac.uk
                Author information
                http://orcid.org/0000-0001-5557-7665
                http://orcid.org/0000-0002-6082-4437
                http://orcid.org/0000-0002-6982-4660
                http://orcid.org/0000-0001-8626-2148
                Article
                gkx1134
                10.1093/nar/gkx1134
                5753285
                29145643
                2e6396e7-ab54-4f88-a6f8-bfd0e65e00d1
                © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 October 2017
                : 17 October 2017
                : 28 September 2017
                Page count
                Pages: 9
                Categories
                Database Issue

                Genetics
                Genetics

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