Saporin
| Saporin | ||
|---|---|---|
| Identifier | ||
| Gene name (s) | SAP1, SAP2, SAP3, SAP4, SAP5, SAP6, SAP7, SAP9 | |
| External IDs | ||
| Enzyme classification | ||
| EC, category | 3.2.2.22 , glycosidase | |
| Response type | Hydrolysis of a special glycoside bond in 28S rRNA | |
| Substrate | 28S rRNA | |
| Products | defective 28S rRNA | |
| Occurrence | ||
| Parent taxon | Saponaria officinalis | |
Saporin is a plant-based, poisonous protein compound ( protein toxin ). It is produced from the common soap herb, Saponaria officinalis , and can be obtained from this plant.
description
Saporin consists of a single polypeptide chain and is produced by the plant in at least ten isoforms , which differ in the amino acid sequence and glycosylation, with an absolute molecular weight of around 27,000 to 30,000 Da . Saporin belongs to the group of plant ribosome-inactivating proteins (RIPs), the protein biosynthesis inactivate especially of mammalian cells.
effect
Saporin cleaves adenine from the 28S ribosomal rRNA and is therefore referred to as N- glycosidase . The adenine of the 28S rRNA is split off at adenine 4324. As a result, the protein biosynthesis of the cell is stopped and the cell dies. However, the N-glycosidase activity is not limited to the 28S rRNA , but also enables adenine to be released from other RNAs and also from DNA .
Saporin consists of only one polypeptide chain and is therefore referred to as type 1 RIP. In contrast, in type 2 RIPs, such as ricin , the receptor- binding domain is located on a second polypeptide chain , the so-called B chain. In contrast, no such receptor-binding domain has been described for saporin. The uptake in cells has not been clearly established for saporin. The intracellular transport of saporin obviously deviates from the route described for ricin, since it is not transported through endosomes to the endoplasmic reticulum in order to get into the cytosol .
use
Due to its high cytotoxic effect, saporin is being tested as a component of immunotoxins and chimeric toxins for the possible treatment of tumors . The DNA sequence coding for saporin is known and therefore allows the recombinant expression of saporin and saporin fusion proteins .
Individual evidence
- ↑ Barthelemy, I., The expression of saporin, a ribosome-inactivating protein from the plant Saponaria officinalis, in Escherichia coli., J Biol Chem (1993), 268 (9): 6541-6548
- ↑ Barbieri, L., Polynucleotide: adenosine glycosidase activity of saporin-L1: effect on various forms of mammalian DNA., Biochim Biophys Acta (2000), 1480 (1-2): 258-266
- ↑ Stirpe, F., Modification of ribosomal RNA by ribosome-inactivating proteins from plants., Nucleic Acids Res (1988), 16 (4): 1349-1357
- ↑ Heisler, I., A colorimetric assay for the quantitation of free adenine applied to determine the enzymatic activity of ribosome-inactivating proteins., Anal Biochem (2002), 302 (1): 114-122
- ↑ Vago, R., Saporin and ricin A chain follow different intracellular routes to enter the cytosol of intoxicated cells., FEBS J (2005), 272 (19): 4983-4995
- ↑ Bachran, C., The saponin-mediated enhanced uptake of targeted saporin-based drugs is strongly dependent on the saponin's structure., Exp Biol Med (2006), 231 (4): 412-420