The Experts below are selected from a list of 324 Experts worldwide ranked by ideXlab platform
Neil D. Rawlings - One of the best experts on this subject based on the ideXlab platform.
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How to use the Merops database and website to help understand peptidase specificity.
Protein science : a publication of the Protein Society, 2020Co-Authors: Neil D. Rawlings, Alex BatemanAbstract:The Merops website (https://www.ebi.ac.uk/Merops) and database was established in 1996 to present the classification and nomenclature of proteolytic enzymes. This was expanded to include a classification of protein inhibitors of proteolytic enzymes in 2004. Each peptidase or inhibitor is assigned to a distinct identifier, based on its biochemical and biological properties, and homologous sequences are assembled into a family. Families in which the proteins share similar tertiary structures are assembled into a clan. The Merops classification is thus a hierarchy with at least three levels (protein-species, family, and clan) showing the evolutionary relationship. Several other data collections have been assembled, which are accessed from all levels in the hierarchy. These include, sequence homologs, selective bibliographies, substrate cleavage sites, peptidase-inhibitor interactions, alignments, and phylogenetic trees. The substrate cleavage collection has been assembled from the literature and includes physiological, pathological, and nonphysiological cleavages in proteins, peptides, and synthetic substrates. In this article, we make recommendations about how best to analyze these data and show analyses to indicate peptidase binding site preferences and exclusions. We also identify peptidases where co-operative binding occurs between adjacent binding sites.
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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
Nucleic acids research, 2017Co-Authors: Neil D. Rawlings, Alan J. Barrett, Alex Bateman, Paul D. Thomas, Xiaosong Huang, Robert D. FinnAbstract: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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Using the Merops Database for Investigation of Lysosomal Peptidases, Their Inhibitors, and Substrates.
Methods in molecular biology (Clifton N.J.), 2017Co-Authors: Neil D. RawlingsAbstract:This chapter describes how to retrieve data on lysosomal peptidases from the Merops database for proteolytic enzymes, their substrates and inhibitors ( http://Merops.sanger.ac.uk ). Features described in this chapter include the summary page, pages for structure, interactions with inhibitors, substrates, literature and involvement in physiological pathways, and how to download data from the Merops FTP site. The lysosomal peptidase legumain is used as an example.
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Current Protocols in Bioinformatics - Using the Merops Database for Proteolytic Enzymes and Their Inhibitors and Substrates.
Current protocols in bioinformatics, 2014Co-Authors: Neil D. Rawlings, Alan J. Barrett, Alex BatemanAbstract:Merops is a database of proteolytic enzymes as well as their inhibitors and substrates. Proteolytic enzymes and protein inhibitors are organized into protein domain families. In turn, families are organized into clans. Each peptidase, inhibitor, family, and clan has associated annotation, a multiple sequence alignment, a phylogenetic tree, literature references, and links to other databases. Interactions between proteolytic enzymes and inhibitors and between proteolytic enzymes and substrates are also presented. The entries in Merops are available via the World Wide Web. This unit contains detailed information on how to access and utilize the information present in the Merops database. Details on running Merops both remotely and locally are presented. © 2014 by John Wiley & Sons, Inc. Keywords: proteolytic enzyme; peptidase; protease; inhibitor; substrate
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using the Merops database for proteolytic enzymes and their inhibitors and substrates
Current protocols in human genetics, 2014Co-Authors: Neil D. Rawlings, Alan J. Barrett, Alex BatemanAbstract:Merops is a database of proteolytic enzymes as well as their inhibitors and substrates. Proteolytic enzymes and protein inhibitors are organized into protein domain families. In turn, families are organized into clans. Each peptidase, inhibitor, family, and clan has associated annotation, a multiple sequence alignment, a phylogenetic tree, literature references, and links to other databases. Interactions between proteolytic enzymes and inhibitors and between proteolytic enzymes and substrates are also presented. The entries in Merops are available via the World Wide Web. This unit contains detailed information on how to access and utilize the information present in the Merops database. Details on running Merops both remotely and locally are presented. © 2014 by John Wiley & Sons, Inc. Keywords: proteolytic enzyme; peptidase; protease; inhibitor; substrate
Alan J. Barrett - One of the best experts on this subject based on the ideXlab platform.
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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
Nucleic acids research, 2017Co-Authors: Neil D. Rawlings, Alan J. Barrett, Alex Bateman, Paul D. Thomas, Xiaosong Huang, Robert D. FinnAbstract: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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Current Protocols in Bioinformatics - Using the Merops Database for Proteolytic Enzymes and Their Inhibitors and Substrates.
Current protocols in bioinformatics, 2014Co-Authors: Neil D. Rawlings, Alan J. Barrett, Alex BatemanAbstract:Merops is a database of proteolytic enzymes as well as their inhibitors and substrates. Proteolytic enzymes and protein inhibitors are organized into protein domain families. In turn, families are organized into clans. Each peptidase, inhibitor, family, and clan has associated annotation, a multiple sequence alignment, a phylogenetic tree, literature references, and links to other databases. Interactions between proteolytic enzymes and inhibitors and between proteolytic enzymes and substrates are also presented. The entries in Merops are available via the World Wide Web. This unit contains detailed information on how to access and utilize the information present in the Merops database. Details on running Merops both remotely and locally are presented. © 2014 by John Wiley & Sons, Inc. Keywords: proteolytic enzyme; peptidase; protease; inhibitor; substrate
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using the Merops database for proteolytic enzymes and their inhibitors and substrates
Current protocols in human genetics, 2014Co-Authors: Neil D. Rawlings, Alan J. Barrett, Alex BatemanAbstract:Merops is a database of proteolytic enzymes as well as their inhibitors and substrates. Proteolytic enzymes and protein inhibitors are organized into protein domain families. In turn, families are organized into clans. Each peptidase, inhibitor, family, and clan has associated annotation, a multiple sequence alignment, a phylogenetic tree, literature references, and links to other databases. Interactions between proteolytic enzymes and inhibitors and between proteolytic enzymes and substrates are also presented. The entries in Merops are available via the World Wide Web. This unit contains detailed information on how to access and utilize the information present in the Merops database. Details on running Merops both remotely and locally are presented. © 2014 by John Wiley & Sons, Inc. Keywords: proteolytic enzyme; peptidase; protease; inhibitor; substrate
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Merops: the database of proteolytic enzymes, their substrates and inhibitors.
Nucleic acids research, 2013Co-Authors: Neil D. Rawlings, Alan J. Barrett, Matthew Waller, Alex BatemanAbstract:Peptidases, their substrates and inhibitors are of great relevance to biology, medicine and biotechnology. The Merops database (http://Merops.sanger.ac.uk) aims to fulfill the need for an integrated source of information about these. The database has hierarchical classifications in which homologous sets of peptidases and protein inhibitors are grouped into protein species, which are grouped into families, which are in turn grouped into clans. Recent developments include the following. A community annotation project has been instigated in which acknowledged experts are invited to contribute summaries for peptidases. Software has been written to provide an Internet-based data entry form. Contributors are acknowledged on the relevant web page. A new display showing the intron/exon structures of eukaryote peptidase genes and the phasing of the junctions has been implemented. It is now possible to filter the list of peptidases from a completely sequenced bacterial genome for a particular strain of the organism. The Merops filing pipeline has been altered to circumvent the restrictions imposed on non-interactive blastp searches, and a HMMER search using specially generated alignments to maximize the distribution of organisms returned in the search results has been added.
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Merops: the database of proteolytic enzymes, their substrates and inhibitors.
Nucleic acids research, 2011Co-Authors: Neil D. Rawlings, Alan J. Barrett, Alex BatemanAbstract:Peptidases, their substrates and inhibitors are of great relevance to biology, medicine and biotechnology. The Merops database (http://Merops.sanger.ac.uk) aims to fulfil the need for an integrated source of information about these. The database has hierarchical classifications in which homologous sets of peptidases and protein inhibitors are grouped into protein species, which are grouped into families, which are in turn grouped into clans. The database has been expanded to include proteolytic enzymes other than peptidases. Special identifiers for peptidases from a variety of model organisms have been established so that orthologues can be detected in other species. A table of predicted active-site residue and metal ligand positions and the residue ranges of the peptidase domains in orthologues has been added to each peptidase summary. New displays of tertiary structures, which can be rotated or have the surfaces displayed, have been added to the structure pages. New indexes for gene names and peptidase substrates have been made available. Among the enhancements to existing features are the inclusion of small-molecule inhibitors in the tables of peptidase-inhibitor interactions, a table of known cleavage sites for each protein substrate, and tables showing the substrate-binding preferences of peptidases derived from combinatorial peptide substrate libraries.
Alex Bateman - One of the best experts on this subject based on the ideXlab platform.
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How to use the Merops database and website to help understand peptidase specificity.
Protein science : a publication of the Protein Society, 2020Co-Authors: Neil D. Rawlings, Alex BatemanAbstract:The Merops website (https://www.ebi.ac.uk/Merops) and database was established in 1996 to present the classification and nomenclature of proteolytic enzymes. This was expanded to include a classification of protein inhibitors of proteolytic enzymes in 2004. Each peptidase or inhibitor is assigned to a distinct identifier, based on its biochemical and biological properties, and homologous sequences are assembled into a family. Families in which the proteins share similar tertiary structures are assembled into a clan. The Merops classification is thus a hierarchy with at least three levels (protein-species, family, and clan) showing the evolutionary relationship. Several other data collections have been assembled, which are accessed from all levels in the hierarchy. These include, sequence homologs, selective bibliographies, substrate cleavage sites, peptidase-inhibitor interactions, alignments, and phylogenetic trees. The substrate cleavage collection has been assembled from the literature and includes physiological, pathological, and nonphysiological cleavages in proteins, peptides, and synthetic substrates. In this article, we make recommendations about how best to analyze these data and show analyses to indicate peptidase binding site preferences and exclusions. We also identify peptidases where co-operative binding occurs between adjacent binding sites.
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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
Nucleic acids research, 2017Co-Authors: Neil D. Rawlings, Alan J. Barrett, Alex Bateman, Paul D. Thomas, Xiaosong Huang, Robert D. FinnAbstract: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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Current Protocols in Bioinformatics - Using the Merops Database for Proteolytic Enzymes and Their Inhibitors and Substrates.
Current protocols in bioinformatics, 2014Co-Authors: Neil D. Rawlings, Alan J. Barrett, Alex BatemanAbstract:Merops is a database of proteolytic enzymes as well as their inhibitors and substrates. Proteolytic enzymes and protein inhibitors are organized into protein domain families. In turn, families are organized into clans. Each peptidase, inhibitor, family, and clan has associated annotation, a multiple sequence alignment, a phylogenetic tree, literature references, and links to other databases. Interactions between proteolytic enzymes and inhibitors and between proteolytic enzymes and substrates are also presented. The entries in Merops are available via the World Wide Web. This unit contains detailed information on how to access and utilize the information present in the Merops database. Details on running Merops both remotely and locally are presented. © 2014 by John Wiley & Sons, Inc. Keywords: proteolytic enzyme; peptidase; protease; inhibitor; substrate
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using the Merops database for proteolytic enzymes and their inhibitors and substrates
Current protocols in human genetics, 2014Co-Authors: Neil D. Rawlings, Alan J. Barrett, Alex BatemanAbstract:Merops is a database of proteolytic enzymes as well as their inhibitors and substrates. Proteolytic enzymes and protein inhibitors are organized into protein domain families. In turn, families are organized into clans. Each peptidase, inhibitor, family, and clan has associated annotation, a multiple sequence alignment, a phylogenetic tree, literature references, and links to other databases. Interactions between proteolytic enzymes and inhibitors and between proteolytic enzymes and substrates are also presented. The entries in Merops are available via the World Wide Web. This unit contains detailed information on how to access and utilize the information present in the Merops database. Details on running Merops both remotely and locally are presented. © 2014 by John Wiley & Sons, Inc. Keywords: proteolytic enzyme; peptidase; protease; inhibitor; substrate
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Merops: the database of proteolytic enzymes, their substrates and inhibitors.
Nucleic acids research, 2013Co-Authors: Neil D. Rawlings, Alan J. Barrett, Matthew Waller, Alex BatemanAbstract:Peptidases, their substrates and inhibitors are of great relevance to biology, medicine and biotechnology. The Merops database (http://Merops.sanger.ac.uk) aims to fulfill the need for an integrated source of information about these. The database has hierarchical classifications in which homologous sets of peptidases and protein inhibitors are grouped into protein species, which are grouped into families, which are in turn grouped into clans. Recent developments include the following. A community annotation project has been instigated in which acknowledged experts are invited to contribute summaries for peptidases. Software has been written to provide an Internet-based data entry form. Contributors are acknowledged on the relevant web page. A new display showing the intron/exon structures of eukaryote peptidase genes and the phasing of the junctions has been implemented. It is now possible to filter the list of peptidases from a completely sequenced bacterial genome for a particular strain of the organism. The Merops filing pipeline has been altered to circumvent the restrictions imposed on non-interactive blastp searches, and a HMMER search using specially generated alignments to maximize the distribution of organisms returned in the search results has been added.
Klaus R. Liedl - One of the best experts on this subject based on the ideXlab platform.
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Protease Inhibitors in View of Peptide Substrate Databases.
Journal of chemical information and modeling, 2016Co-Authors: Birgit J. Waldner, Julian E. Fuchs, Michael Schauperl, Christian Kramer, Klaus R. LiedlAbstract:Protease substrate profiling has nowadays almost become a routine task for experimentalists, and the knowledge on protease peptide substrates is easily accessible via the Merops database. We present a shape-based virtual screening workflow using vROCS that applies the information about the specificity of the proteases to find new small-molecule inhibitors. Peptide substrate sequences for three to four substrate positions of each substrate from the Merops database were used to build the training set. Two-dimensional substrate sequences were converted to three-dimensional conformations through mutation of a template peptide substrate. The vROCS query was built from single amino acid queries for each substrate position considering the relative frequencies of the amino acids. The peptide-substrate-based shape-based virtual screening approach gives good performance for the four proteases thrombin, factor Xa, factor VIIa, and caspase-3 with the DUD-E data set. The results show that the method works for protease...
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Protease Inhibitors in View of Peptide Substrate Databases
2016Co-Authors: Birgit J. Waldner, Julian E. Fuchs, Michael Schauperl, Christian Kramer, Klaus R. LiedlAbstract:Protease substrate profiling has nowadays almost become a routine task for experimentalists, and the knowledge on protease peptide substrates is easily accessible via the Merops database. We present a shape-based virtual screening workflow using vROCS that applies the information about the specificity of the proteases to find new small-molecule inhibitors. Peptide substrate sequences for three to four substrate positions of each substrate from the Merops database were used to build the training set. Two-dimensional substrate sequences were converted to three-dimensional conformations through mutation of a template peptide substrate. The vROCS query was built from single amino acid queries for each substrate position considering the relative frequencies of the amino acids. The peptide-substrate-based shape-based virtual screening approach gives good performance for the four proteases thrombin, factor Xa, factor VIIa, and caspase-3 with the DUD-E data set. The results show that the method works for protease targets with different specificity profiles as well as for targets with different active-site mechanisms. As no structure of the target and no information on small-molecule inhibitors are required to use our approach, the method has significant advantages in comparison with conventional structure- and ligand-based methods
Robert Heinsohn - One of the best experts on this subject based on the ideXlab platform.
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Microsatellite loci for behavioural studies of rainbow bee-eaters (Merops ornatus: Aves)
Molecular Ecology Notes, 2006Co-Authors: Gregory J. Adcock, Kathryn Hodges, Christopher R. J. Boland, Andrew Cockburn, Daniel Ebert, Robert HeinsohnAbstract:A set of polymorphic microsatellite loci was identified for population and behavioural studies of the rainbow bee-eater ( Merops ornatus ). Eight loci were newly isolated from a rainbow bee-eater genomic library enriched for GA-containing repeats, and six loci from those previously reported for the European bee-eater ( Merops apiaster ). From these two sources, the seven most variable loci that amplified reliably were unlinked and in Hardy–Weinberg equilibrium, had five to 13 alleles (mean 7.7) and an expected heterozygosity of 0.60–0.86 (mean 0.73).