Archive for the 'Uncategorized' Category


April 29, 2010

Changes to Small Molecule Inhibitor displays

A unique identifier for each small molecule inhibitor (SMI) has been introduced. The identifier is the letter J followed by by a five-digit number. These are displayed on the SMI summaries, the SMI index and the inhibitors pages in the peptidase summaries. Cross-references to the University of Alberta’s DrugBank database are now included on the SMI summary pages. Interactions between peptidases and SMIs are now included on the inhibitors pages. This includes not only SMIs for which we have summaries and identifiers, but also other SMIs.

Sequence features

A new page has been added to each peptidase and inhibitor summary to display our predictions of active site residues (peptidases only), metal ligands (metallopeptidases only), extent of the peptidase or inhibitor unit, sequence length, and the source of the sequence used in MEROPS with a link to the relevant primary sequence database.

Changes to substrate displays

It is now possible to filter the list of substrates cleaved by a peptidase to limit the display to either protein and peptide substrates of physiological relevance, proteins and peptide substrates that are not physiologically relevance, or synthetic substrates.

Links to Wikipedia entries

There are now links from peptidase and inhibitor summaries to Wikipedia entries. There is considerable extra data on a peptidase or an inhibitor in Wikipedia because of the effort Wikipedia users have put in to the Molecular and Cellular Biology WikiProject. We at MEROPS encourage our users to register at Wikipedia and to contribute to existing pages and create new pages for peptidases and their inhibitors.


January 26, 2010

New data release

This is second half of the release that began in December 2009 when all the software was updated. In this release the data have been updated. In future, software and data will be updated simultaneously.

Links to ChEMBL

Links to the ChEMBL database have been added. These are links to drug targets in ChEMBL and can be found on the pharma pages at the peptidase level.

Problems with the new codebase

We apologize that the software update in December did not go smoothly, and several aspects of the MEROPS website were either not working, not working properly or missing. Most of these problems have been fixed and we would like to thank the users who pointed out problems of which we were unaware. There are still issues to be resolved with the MEROPS batch Blast and the dynamic alignments and trees.


December 24, 2009

The release of MEROPS 9 was more complex than had been realised, and it has taken a few days to get everything working.  We apologise for any pages, features or facilities that have been missing.  If you notice any pages, features or facilities that are not working properly then please let us know, preferably via the new feedback system.


December 24, 2009

New codebase Release 9 of MEROPS will be in two parts. The reason for this is that the software that produces the web pages has been re-written by Matthew Waller and Jody Clements from the Wellcome Trust Sanger Institute web team. In January 2010 the new data will be published. The release has been done in this way so that any programming bugs can be detected and reliably separated from data errors. The FTP site will also be updated in January. The new software has been designed to resemble the old website, and the changes have mainly been for our benefit, to simplify the maintainence and make it easier to add new features. Users will notice that frames have disappeared, and that the left-hand green menu now scrolls with the rest of the page. Links to external databases now open in the same window so you will have to use the back button to return to MEROPS. References and sequences are now displayed in small windows in the middle of the screen.

Feedback and reporting errors

The MEROPS website now has a ticketing system for reporting errors and making comments. Each page now has a feedback link in the footer. The user will be asked to enter his or her name and an E-mail address when the comment is posted. The user will receive an automated E-mail which should not be replied to. A member of the MEROPS team will then contact the user and when the problem has been fixed the ticket will be closed. The user will receive a second automated E-mail. This should only be replied to if the issue has not been resolved to the user’s satisfaction: the ticket will then be automatically re-opened. Please use this system to report programming errors, broken links and any errors or omissions in the data.

Links to PubMed Central from Literature pages

There are now links from the clan, family, peptidase and inhibitor literature pages to the full text of papers stored in PubMed Central.


December 24, 2009

Domain images and architecture pages
We have redesigned the domain images which appear on the peptidase summaries.  Each image is scaled according to the sequence length, shown as a blue line.  The peptidase unit is shown as a green box, with the active site residues and metal legands (if any) shown as red and blue “lollipops”,respectively, along the bottom edge of the box.  The top edge shows disulfide bridges, and known carbohydrate binding sites (as orange lollipops).  An inhibitor uint is shown as a large, grey box, with reactive site residues shown on the bottom edge as red lollipops.  Other domains that have been annotated by SwissProt or Pfam are shown as smaller boxes.  Domains derived from Pfam are shown as red boxes and links to the Pfam database can be accessed by clicking on the domain.  Signal peptides and transmembrane domains are shown as small, black boxes.  Propeptides are shown as small, grey boxes.  Mouse-over text gives details for each feature displayed.

Because these simpler domain images are quicker to generate, we now include at the family level a page showing the different protein architectures known in the family or subfamily, ordered by MEROPS identifier.

Comparisons of peptidase specificity

The MEROPS collection of substrate cleavages now exceeds 38,500.  There are over three hundred peptidases for which ten or more substrates are known.  In addition to the displays on a peptidase summary, MEROPS now includes displays to compare preferences in binding pockets S4 to S4′.  These are items on the substrate index and show preference in terms of all amino acids, amino acid properties and individual amino acids.  The first of these shows, for each peptidase, an amino acid if it occurs in the same binding pocket in 40% or more of the substrates.  So no more than two amino acids are shown for any one binding pocket. The amino acid is shown with a green background, and the brighter the green the greater the percentage of substrates with the amino acid in that binding pocket.  The second display is similar but instead of showing individual amino acids, these are collected into “aliphatic”, “aromatic”, “acidic”, “basic” or “small” groups.  In the third option the user is prompted to select an amino acid from a pull-down menu and the displays shows the number of substrates with the selected amino acid in each binding pocket for each peptidase.  Where an amino acid has not been observed in a binding pocket, this is hightlighted in black.  In all three displays where no amino acid is possible (for example P4, P3 and P2 for an aminopeptidase, of P2′, P3′ or P4′ for a carboxypeptidase) the binding pocket is highlighted in grey.

Substrate alignments
If known, the substrate alignments how show protein secondary structure at the foot of the alignment.  A helix is shown as a string of “a’s” and is highlighted in red, a beta strand is shown as a string of “b’s” and is highlighted in green.

MEROPS identifiers for another model organism
We recently expanded MEROPS identifiers to Arabidopsis thaliana, as well as human, mouse and rat, so that every gene product that is likely to be a peptidase has a unique identifier.  We have now added identifiers for all probable peptidase in Saccharomyces cerevisiae.  Identifiers for peptidases for this organism have the first character after the dot replaced by the letter A.  When a homologue is characterized biochemically, we will replace the identifier with one in the standard format (three digits after the dot).

Richardson diagrams
The number of Richardson diagrams showing cartoons of structures has substantially increased, thanks to the hard work of Matthew Jenner, who has been working with us this summer.  There is now a Richardson diagram for every peptidase or inhibitor for which a tertiary structure has been solved.

Predicted sequences from the chimpanzee genome
Summer student Matthew Jenner has also been predicting protein sequences from the chimpanzee genome.  Protein sequences from eukaryote genomes are collected from the Ensembl database.  Although Ensembl has a sophisticated, automated pipeline for predicting protein sequences, some predictions require a further manual stage.  These are predictions where exons are missed, introns are mistranslated as exons, or genes are run together.  Predicted protein sequences derived from orthologue genes which show the greatest difference between human and chimpanzee have been recalculated using the GeneWise software, the human sequence as a template and nucleotide sequence found in the chimpanzee genome by using the Ensembl Blast search service.

Bug fixes

April 15, 2009

The following bugs have been fixed:

  • Substrate alignment display: highlighting of conserved and preferred residues has been corrected for the unusual situation where the sequence of the protein with known cleavages started at position 1 in the alignment; i.e. there were no other sequences with N-terminal extentions.  Previously highlighting had been one residue out.
  • Specificity heatmap: the shades of green in this display have been altered.  Previously highlighting for residues occurring in more than 40% of cleavages but less than 50% for a particular position (P4 to P4′) was too dark and indistinguishable from the black background indicating no preference.
  • Peptidase distribution display: the bug that was preventing several tree tip labels from being highlighted has been fixed. 


April 15, 2009

MEROPS 8.4 was released on 3 April 2009. New features include the following:

Substrate indexes
Two indexes for peptidase substrates have been added. These are accessible from the left-hand green menu. The first index shows the count of known substrate cleavages per peptidase, ordered by and linked to the MEROPS identifier. Three counts are shown: the total number in the MEROPS collection, the total number of physiological substrates (peptides and proteins) and the total number of non-physiological substrates (peptides and synthetic substrates). The second index is ordered by substrate name and shows the MEROPS identifier of the peptidases known to cleave each substrate and the total number of cleavages performed by each peptidase. For substrates than can be mapped to the UniProt protein sequence database the UniProt identifier is shown with a link to the MEROPS utility which shows all cleavages of this protein in the MEROPS collection.

Substrate pages
We have introduced “flags” on the substrate pages to indicate the method used to identify the cleavage position. The flags are as follows: NT shows that the cleavage position was determined by N-Terminal sequencing, MS shows that the peptide composition was determined by mass-spectroscopy (MS) and the cleavage position computed, MU shows that the cleavage position was determined by site-directed MUtagenesis, CS indicates that the cleavage position was postulated from a concensus motif (CS) within the protein sequence.

Release of signal and transit peptides and initiating methionine
Cleavages that result in the release of signal and transit peptides and the initiating methionine have been automatically collected from the annotations in the SwissProt protein sequence database. However, cleavages were not previously assigned to a specific MEROPS identifier. This has now changed, and assignments made where possible. Such assignments can only be made for organisms where the genome has been completely sequenced and only one homologue is known from the family in question. Data for the cleavage position is usually determined by N-terminal sequencing, but readers should be aware that at least for chloroplast transit peptides, aminopeptidases are also transported into the chloroplast which may remove amino acids from proteins subsequent to the removal of the transit peptides.

Pharma pages
For peptidases that are drug targets we are now collecting links to databases of interest to the pharmaceutical industry. These are collected together on the new Pharma pages accessible for the peptidase summary. We are currently making links to the PubChem BioAssay database and the Binding Database.

Literature flags
Several new flags have been added to the Literature pages. The full list of flags is:

A Assay method,
E recombinant Expression,
I design of small-molecule Inhibitors,
K gene Knockout or other artificial genetic manipulation,
M natural Mutation, allelic variant or polymorphism,
P Substrate specificity,
R RNA splice variation,
S three-dimensional Structure,
T proposed as a therapeutic Target,
U suggested to have therapeutic potential itself,
V Review.

Structure pages
Structure pages now include a link to Proteopedia.

Welcome to the MEROPS blog

January 22, 2009

Welcome to the MEROPS blog.  This is a forum to announce new releases of the MEROPS databases and to get feedback from our users for matters concerning the classification and nomenclature of peptidases, their substrates and inhibitors.