Medizinische Fakultät der Universität des Saarlandes
Humangenetik
Leitung: Prof. Dr. Eckart Meese
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Humangenetik

A software tool for predicting granzyme B and caspase cleavage sites

Abstract:

Caspases and granzyme B are proteases that share the primary specificity to cleave at the carboxyl terminal of aspartate residues in their substrates. Both, caspases and granzyme B are enzymes that are involved in fundamental cellular processes and play a central role in apoptotic cell death. Although various targets are described, many substrates still await identification and many cleavage sites of known substrates are not identified or experimentally verified. Here, we present a tool "GraBCas" that provides score-based prediction of potential cleavage sites for the caspases 1-9 and granzyme B including an estimation of the fragment size.

 

 

Download:

This tool is written in Java and available as an application.


If your browser doesn't support Java you need to install the Java© Runtime Environment (JRE) Version 1.4.x, which you can download here .


If you want to use GraBCas as an application you need to download the jar-file. Type the following in a command line:
java -jar GraBCas.jar

Usage:

The program is signed with a self-certified signature to allow the applet "copy&paste" permissions. After starting the program or applet a security dialog will pop up explaining who signed the applet and provide four options:

  • Grant this session: If selected, the applet will be granted "copy&paste" permission. Every applet restart will be trusted automatically within the same browser session.

  • Deny: If selected, the applet will not start.

  • Grant always: If selected, the applet will be granted "copy&paste" permission. Every applet restart will be trusted in future, and no security dialog will pop up again.

  • More Info: If selected, users can examine the attributes of the certificate.

 

To paste text from the system clipboard you can use on every system (Mac, Unix and Win) 

ctr-v

in the input form. Paste an amino acid sequence in capital letters (without fasta header) into the input form and choose a score cutoff. Press the OK-button, and the program will compute the cleavage sites for granzyme B and caspase 1-9. The output for each enzyme is presented on separated register cards. The scoring ranges from 0-100 with 100 being identical to the consensus recognition motif of the corresponding endopetidase. Proposed cleavage sites are computed based on the similarity to the consensus recognition motif that is based on experimental data of Thornberry et al. (1997). Our approach is illustrated by the following example for a possible cleavage site "VPLD" for Granzyme B: 

 

The distribution of the possible cleavage sites in the amino acid sequence and their estimated molecular weight are also indicated by request. Two optional filters for granzyme B and caspase 3, both of them based on data of known cleavage sites, allow consideration of additional amino acids.