The Experts below are selected from a list of 309 Experts worldwide ranked by ideXlab platform
Neil D. Rawlings - One of the best experts on this subject based on the ideXlab platform.
-
Origins of Peptidases.
Biochimie, 2019Co-Authors: Neil D. Rawlings, Alex BatemanAbstract:The distribution of all Peptidase homologues across all phyla of organisms was analysed to determine within which kingdom each of the 271 families originated. No family was found to be ubiquitous and even Peptidases thought to be essential for life, such as signal Peptidase and methionyl aminopeptides are missing from some clades. There are 33 Peptidase families common to archaea, bacteria and eukaryotes and are assumed to have originated in the last universal common ancestor (LUCA). These include Peptidases with different catalytic types, exo- and endoPeptidases, Peptidases with different tertiary structures and Peptidases from different families but with similar structures. This implies that the different catalytic types and structures pre-date LUCA. Other families have had their origins in the ancestors of viruses, archaea, bacteria, fungi, plants and animals, and a number of families have had their origins in the ancestors of particular phyla. The evolution of Peptidases is compared to recent hypotheses about the evolution of organisms.
-
twenty years of the merops database of proteolytic enzymes their substrates and inhibitors
Nucleic Acids Research, 2016Co-Authors: Neil D. Rawlings, Alan J. Barrett, Robert D FinnAbstract:: The MEROPS database (http://merops.sanger.ac.uk) is an integrated source of information about Peptidases, their substrates and inhibitors, which are of great relevance to biology, medicine and biotechnology. The hierarchical classification of the database is as follows: homologous sets of sequences are grouped into a protein species; protein species are grouped into a family; families are grouped into clans. There is a type example for each protein species (known as a 'holotype'), family and clan, and each protein species, family and clan has its own unique identifier. Pages to show the involvement of Peptidases and Peptidase inhibitors in biological pathways have been created. Each page shows the Peptidases and Peptidase inhibitors involved in the pathway, along with the known substrate cleavages and Peptidase-inhibitor interactions, and a link to the KEGG database of biological pathways. Links have also been established with the IUPHAR Guide to Pharmacology. A new service has been set up to allow the submission of identified substrate cleavages so that conservation of the cleavage site can be assessed. This should help establish whether or not a cleavage site is physiologically relevant on the basis that such a cleavage site is likely to be conserved.
-
Introduction: aspartic Peptidases and their clans
Handbook of Proteolytic Enzymes, 2012Co-Authors: Neil D. Rawlings, Alan J. BarrettAbstract:Publisher Summary This chapter presents an introduction to aspartic Peptidases and their clans. Aspartic Peptidases are so named because Asp residues are ligands of the activated water molecule. In the great majority of known aspartic Peptidases, a pair of aspartic residues act together to bind and activate the catalytic water molecule, but in some, residues of other amino acids replace the second Asp. Aspartic Peptidases are assigned to clans AA, AB, AC, AD and AF. Tertiary structures solved for members of clans AA, AB and AF each show a unique protein fold unrelated to that of any other Peptidase. For clans AC and AD, there is no crystal structure yet, but other criteria point to their distinctiveness. The clans and the families of aspartic Peptidases are summarized in the chapter. The Peptidases of family Al are found only in eukaryotes and like all aspartic Peptidases, they are endoPeptidases. The great majority are most active at acidic pH, but a few show an activity under neutral conditions.
-
Peptidase inhibitors in the MEROPS database.
Biochimie, 2010Co-Authors: Neil D. RawlingsAbstract:The MEROPS website (http://merops.sanger.ac.uk) includes information on Peptidase inhibitors as well as on Peptidases and their substrates. Displays have been put in place to link Peptidases and inhibitors together. The classification of protein Peptidase inhibitors is continually being revised, and currently inhibitors are grouped into 67 families based on comparisons of protein sequences. These families can be further grouped into 38 clans based on comparisons of tertiary structure. Small molecule inhibitors are important reagents for Peptidase characterization and, with the increasing importance of Peptidases as drug targets, they are also important to the pharmaceutical industry. Small molecule inhibitors are now included in MEROPS and over 160 summaries have been written.
-
MEROPS: the Peptidase database
Nucleic Acids Research, 2009Co-Authors: Neil D. Rawlings, Dominic P. Tolle, Alan J. BarrettAbstract:Peptidases (proteolytic enzymes) are of great relevance to biology, medicine and biotechnology. This practical importance creates a need for an integrated source of information about them, and also about their natural inhibitors. The MEROPS database (http://merops.sanger.ac.uk) aims to fill this need. The organizational principle of the database is a hierarchical classification in which homologous sets of the proteins of interest are grouped in families and the homologous families are grouped in clans. Each Peptidase, family and clan has a unique identifier. The database has recently been expanded to include the protein inhibitors of Peptidases, and these are classified in much the same way as the Peptidases. Forms of information recently added include new links to other databases, summary alignments for Peptidase clans, displays to show the distribution of Peptidases and inhibitors among organisms, substrate cleavage sites and indexes for expressed sequence tag libraries containing Peptidases. A new way of making hyperlinks to the database has been devised and a BlastP search of our library of Peptidase and inhibitor sequences has been added.
Alan J. Barrett - One of the best experts on this subject based on the ideXlab platform.
-
twenty years of the merops database of proteolytic enzymes their substrates and inhibitors
Nucleic Acids Research, 2016Co-Authors: Neil D. Rawlings, Alan J. Barrett, Robert D FinnAbstract:: The MEROPS database (http://merops.sanger.ac.uk) is an integrated source of information about Peptidases, their substrates and inhibitors, which are of great relevance to biology, medicine and biotechnology. The hierarchical classification of the database is as follows: homologous sets of sequences are grouped into a protein species; protein species are grouped into a family; families are grouped into clans. There is a type example for each protein species (known as a 'holotype'), family and clan, and each protein species, family and clan has its own unique identifier. Pages to show the involvement of Peptidases and Peptidase inhibitors in biological pathways have been created. Each page shows the Peptidases and Peptidase inhibitors involved in the pathway, along with the known substrate cleavages and Peptidase-inhibitor interactions, and a link to the KEGG database of biological pathways. Links have also been established with the IUPHAR Guide to Pharmacology. A new service has been set up to allow the submission of identified substrate cleavages so that conservation of the cleavage site can be assessed. This should help establish whether or not a cleavage site is physiologically relevant on the basis that such a cleavage site is likely to be conserved.
-
Introduction: aspartic Peptidases and their clans
Handbook of Proteolytic Enzymes, 2012Co-Authors: Neil D. Rawlings, Alan J. BarrettAbstract:Publisher Summary This chapter presents an introduction to aspartic Peptidases and their clans. Aspartic Peptidases are so named because Asp residues are ligands of the activated water molecule. In the great majority of known aspartic Peptidases, a pair of aspartic residues act together to bind and activate the catalytic water molecule, but in some, residues of other amino acids replace the second Asp. Aspartic Peptidases are assigned to clans AA, AB, AC, AD and AF. Tertiary structures solved for members of clans AA, AB and AF each show a unique protein fold unrelated to that of any other Peptidase. For clans AC and AD, there is no crystal structure yet, but other criteria point to their distinctiveness. The clans and the families of aspartic Peptidases are summarized in the chapter. The Peptidases of family Al are found only in eukaryotes and like all aspartic Peptidases, they are endoPeptidases. The great majority are most active at acidic pH, but a few show an activity under neutral conditions.
-
MEROPS: the Peptidase database
Nucleic Acids Research, 2009Co-Authors: Neil D. Rawlings, Dominic P. Tolle, Alan J. BarrettAbstract:Peptidases (proteolytic enzymes) are of great relevance to biology, medicine and biotechnology. This practical importance creates a need for an integrated source of information about them, and also about their natural inhibitors. The MEROPS database (http://merops.sanger.ac.uk) aims to fill this need. The organizational principle of the database is a hierarchical classification in which homologous sets of the proteins of interest are grouped in families and the homologous families are grouped in clans. Each Peptidase, family and clan has a unique identifier. The database has recently been expanded to include the protein inhibitors of Peptidases, and these are classified in much the same way as the Peptidases. Forms of information recently added include new links to other databases, summary alignments for Peptidase clans, displays to show the distribution of Peptidases and inhibitors among organisms, substrate cleavage sites and indexes for expressed sequence tag libraries containing Peptidases. A new way of making hyperlinks to the database has been devised and a BlastP search of our library of Peptidase and inhibitor sequences has been added.
-
MEROPS: the Peptidase database.
Nucleic acids research, 2007Co-Authors: Neil D. Rawlings, Fraser R Morton, Chai Yin Kok, Jun Kong, Alan J. BarrettAbstract:Peptidases (proteolytic enzymes or proteases), 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 organizational principle of the database is a hierarchical classification in which homologous sets of Peptidases and protein inhibitors are grouped into protein species, which are grouped into families and in turn grouped into clans. Important additions to the database include newly written, concise text annotations for Peptidase clans and the small molecule inhibitors that are outside the scope of the standard classification; displays to show Peptidase specificity compiled from our collection of known substrate cleavages; tables of Peptidase-inhibitor interactions; and dynamically generated alignments of representatives of each protein species at the family level. New ways to compare Peptidase and inhibitor complements between any two organisms whose genomes have been completely sequenced, or between different strains or subspecies of the same organism, have been devised.
-
'Species' of Peptidases.
Biological Chemistry, 2007Co-Authors: Alan J. Barrett, Neil D. RawlingsAbstract:A good system for the naming and classification of Peptidases can contribute much to the study of these enzymes. Having already described the building of families and clans in the MEROPS system, we here focus on the lowest level in the hierarchy, in which the huge number of individual Peptidase proteins are assigned to a lesser number of what we term 'species' of Peptidases. Just over 2000 Peptidase species are recognised today, but we estimate that 25 000 will one day be known. Each species is built around a Peptidase protein that has been adequately characterised. The cluster of Peptidase proteins that represent the single species is then assembled primarily by analysis of a sequence 'tree' for the family. Each Peptidase species is given a systematic identifier and a summary page of data regarding it is assembled. Because the characterisation of new Peptidases lags far behind the sequencing, the majority of Peptidase proteins are so far known only as amino acid sequences and cannot yet be assigned to species. We suggest that new forms of analysis of the sequences of the unassigned Peptidases may give early indications of how they will cluster into the new species of the future.
Muhamed-kheir Taha - One of the best experts on this subject based on the ideXlab platform.
-
Type IV prepilin Peptidase
Handbook of Proteolytic Enzymes, 2012Co-Authors: Bruno Dupuy, Ala-eddine Deghmane, Muhamed-kheir TahaAbstract:Publisher Summary This chapter covers the structural chemistry and the biological aspects of type IV prepilin Peptidase. Type IV prepilin Peptidases and type IV prepilin-like Peptidases are homologous over their entire amino acid sequences, and in some but not all cases are interchangeable in vivo . Type IV prepilin Peptidases are located in the cytoplasmic membrane, but have large, relatively hydrophilic domains in the cytoplasm (domain 1). These cytoplasmic domains are the parts of the proteins that are most highly conserved in the type IV prepilin Peptidase family. Because of the inherent difficulties in the purification of integral membrane proteins by conventional methods, the purification of type IV prepilin Peptidase from P. aeruginosa is accomplished by detergent solubilization of the membranes and immunoaffinity chromatography. This method remains the method of choice for obtaining type IV prepilin-like Peptidase in a pure form. One of the more interesting properties of the type IV prepilin Peptidase is its bifunctionality. This protease not only cleaves the leader sequence but also carries out N-terminal methylation of the mature pilin. This Peptidase differs from the two other known signal Peptidases, LepB, the major signal Peptidase, and LspA, the lipoprotein signal Peptidase.
-
Type IV prepilin Peptidase
2004Co-Authors: Bruno Dupuy, Ala-eddine Deghmane, Muhamed-kheir TahaAbstract:This chapter covers the structural chemistry and the biological aspects of type IV prepilin Peptidase. Type IV prepilin Peptidases and type IV prepilin-like Peptidases are homologous over their entire amino acid sequences, and in some but not all cases are interchangeable in vivo. Type IV prepilin Peptidases are located in the cytoplasmic membrane, but have large, relatively hydrophilic domains in the cytoplasm (domain 1). These cytoplasmic domains are the parts of the proteins that are most highly conserved in the type IV prepilin Peptidase family. Because of the inherent difficulties in the purification of integral membrane proteins by conventional methods, the purification of type IV prepilin Peptidase from P. aeruginosa is accomplished by detergent solubilization of the membranes and immunoaffinity chromatography. This method remains the method of choice for obtaining type IV prepilin-like Peptidase in a pure form. One of the more interesting properties of the type IV prepilin Peptidase is its bifunctionality. This protease not only cleaves the leader sequence but also carries out N-terminal methylation of the mature pilin. This Peptidase differs from the two other known signal Peptidases, LepB, the major signal Peptidase, and LspA, the lipoprotein signal Peptidase.
Marcio C Silvafilho - One of the best experts on this subject based on the ideXlab platform.
-
sugarcane serine Peptidase inhibitors serine Peptidases and clp protease system subunits associated with sugarcane borer diatraea saccharalis herbivory and wounding
International Journal of Molecular Sciences, 2016Co-Authors: Ane H Medeiros, Fabiana B Mingossi, Renata O Dias, Flavia P Franco, Renato Vicentini, Marcia O Mello, Daniel S Moura, Marcio C SilvafilhoAbstract:Sugarcane’s (Saccharum spp.) response to Diatraea saccharalis (F.) (Lepidoptera: (Crambidae) herbivory was investigated using a macroarray spotted with 248 sugarcane Expressed Sequence Tags (ESTs) encoding serine Peptidase inhibitors, serine Peptidases. and Clp protease system subunits. Our results showed that after nine hours of herbivory, 13 sugarcane genes were upregulated and nine were downregulated. Among the upregulated genes, nine were similar to serine Peptidase inhibitors and four were similar to Bowman-Birk Inhibitors (BBIs). Phylogenetic analysis revealed that these sequences belong to a phylogenetic group of sugarcane BBIs that are potentially involved in plant defense against insect predation. The remaining four upregulated genes included serine Peptidases and one homolog to the Arabidopsis AAA+ chaperone subunit ClpD, which is a member of the Clp protease system. Among the downregulated genes, five were homologous to serine Peptidases and four were homologous to Arabidopsis Clp subunits (three homologous to Clp AAA+ chaperones and one to a ClpP-related ClpR subunit). Although the roles of serine Peptidase inhibitors in plant defenses against herbivory have been extensively investigated, the roles of plant serine Peptidases and the Clp protease system represent a new and underexplored field of study. The up- and downregulated D. saccharalis genes presented in this study may be candidate genes for the further investigation of the sugarcane response to herbivory.
Alan Saghatelian - One of the best experts on this subject based on the ideXlab platform.
-
Peptidomics of the Prolyl Peptidases
The AAPS Journal, 2010Co-Authors: Anna Mari Lone, Whitney M. Nolte, Arthur D. Tinoco, Alan SaghatelianAbstract:The prolyl Peptidases are a family of enzymes characterized by a biochemical preference for cleaving proline-containing peptides. The members of this enzyme family include prolyl endoPeptidase, prolyl endoPeptidase-like, dipeptidyl Peptidase 4 (DPP4), DPP7, DPP8, DPP9, and fibroblast activation protein. DPP4 is the best studied member of the family, due to its role in physiological glucose tolerance, exerted through the regulation of the insulinotropic peptide glucagon-like peptide-1. While other members of the prolyl Peptidase family have also been implicated in various (patho)physiological processes, the underlying peptides and pathways regulated by these enzymes are less clear. The identification of endogenous substrates of the prolyl Peptidases is an important step in elucidating the molecular mechanisms of these enzymes. Here, we highlight the utility of liquid chromatography–mass spectrometry-based peptidomics to enable the discovery of endogenous prolyl Peptidase substrates directly from tissues, and demonstrate the utility of this information in understanding the biochemical and physiological functions of the prolyl Peptidases.