Saporin

<StructureSection load='1QI7' size='340' side='right' caption='Caption for this structure' scene=''>

Saporin is a ribosome-inactivating protein (RIP); alone, saporin does not selectively inactive ribosomes but rather conjugate with other molecules like peptides <ref name="basel">DOI:

10.3390/toxins12090546</ref>. Saponaria officinalis is the plant from which saporin is extracted <ref name="ncbi">DOI: 10.3390/toxins5101698</ref>. Type I and type II RIPS exist. Of these types, saporin is a type I. Ribosome inactivating proteins catalyze a cleavages N-glycosidic bond that is formed between the ribosome and adenine <ref name="rcsb">DOI: 10.1016/s0014-5793(00)01325-9</ref>. This adenine has the role of binding EF-1 and EF-2 to a ribosome <ref name="rcsb" />. EF stands for elongation factor. Since adenine no longer has a bond to the ribosome, the elongation step in translation cannot occur because the elongation factors cannot bind to just the ribosome. The specific elongation factor that is inhibited is elongation factor 2, which causes irreversible damage and disallows protein synthesis <ref name="ncbi" />.

Type 1 RIPS are monomeric, meaning they have one part <ref name="fab">DOI: 10.3390/toxins9100314</ref>. Saporin-S6 at maturity is 256 amino acids long <ref name="ncbi" />. While saporin consists of different residues and molecules, there is only one Chain A in it, and thus is monomeric. Chain A is a polypeptide weighing 30 KDa <ref name="nano">DOI: 10.3390/cancers12020498</ref>. This chain consists of beta-sheets and alpha-helixes. The β-sheets make up the N-terminal domain, while the 𝛼-helix portion is the C-terminal domain <ref name="rcsb" />. In the figure of Chain A, the 𝛼-helices are spiral-shaped strands, while the β-sheets are more of a flat strand.

There is an active site within this chain that consists of five residues. These residues are Tyr⁷², Tyr¹²⁰, Glu¹⁷⁶, Arg¹⁷⁹, and Trp²⁰⁸ <ref name="ncbi" />. Other RIPs also have these same residues in their active sites. The saporin active has Glu¹⁷⁶, Arg¹⁷⁹, and Trp²⁰⁸ in the exact same position as the other ribosome-inactivating proteins. There is a difference in Tyr⁷², which has different side-chain conformations in RIPs and thus is not the same in saporin and other RIPs. This Tyr⁷² is the residue that interacts with the adenine in the cleavage of adenine and the ribosome <ref name="rcsb" />.

Saporin can also be complexed with other inhibitors. One of these is cyclic tetranucleotide inhibitor in complex with saporin-L1. This can be used because the cyclic tetranucleotide can take the place of the recognition loop for saporin of 28S rRNA <ref name="pnas">DOI: 10.1073/pnas.0911606106</ref>. It is also interesting to note that Ricin can also be complex with other inhibitors like saporin. Saporin is a homologue of Ricin A-Chain which means they are similar in structure <ref name="pnas" />. This ability also allows for saporin-S6 to be conjugated with specific targeting proteins, and thus the saporin-S6 is able to be delivered to the cell. This happens due to the antibodies and is referred to as an immunotoxin <ref name="ncbi" />. The antibodies are recognized by the cell, and the cell binds them. Since the saporin-S6 is in complex with the antibody, it is also taken to the cell. Some other carries can also be used, such as growth factors, antigens, and growth hormones <ref name="ncbi" />.