Pokeweed antiviral protein, a ribosome inactivating protein: activity, inhibition and prospects

• Published in: Toxins Vol. 7; no. 2; pp. 274 - 298
• Main Authors: Domashevskiy, Artem V, Goss, Dixie J
• Format: Journal Article Book Review
• Language: English
• Published: Switzerland MDPI AG 28-01-2015; MDPI
• Subjects: Animals; Binding Sites; Endoribonucleases - chemistry; Fungal Proteins - chemistry; Genome, Viral; Humans; immunotoxin; Immunotoxins; Phytolacca americana; pokeweed antiviral protein; Protein Isoforms; Protein synthesis; Review; ribosome inactivating protein; Ribosome Inactivating Proteins, Type 1 - chemistry; Ribosome Inactivating Proteins, Type 1 - genetics; Ribosome Inactivating Proteins, Type 1 - metabolism; Ribosome Inactivating Proteins, Type 1 - pharmacology; Ribosomes - chemistry; Ribosomes - metabolism; Ricin - chemistry; RNA Caps - chemistry; RNA Caps - genetics; RNA Caps - metabolism; RNA, Plant - chemistry; RNA, Plant - genetics; RNA, Plant - metabolism; RNA, Ribosomal - chemistry; RNA, Ribosomal - genetics; RNA, Ribosomal - metabolism; RNA, Viral - chemistry; RNA, Viral - genetics; RNA, Viral - metabolism; sarcin/ricin loop; Toxins; Translocation; virus genome-linked protein
• ISSN: 2072-6651; 2072-6651
• DOI: 10.3390/toxins7020274

Viruses employ an array of elaborate strategies to overcome plant defense mechanisms and must adapt to the requirements of the host translational systems. Pokeweed antiviral protein (PAP) from Phytolacca americana is a ribosome inactivating protein (RIP) and is an RNA N-glycosidase that removes specific purine residues from the sarcin/ricin (S/R) loop of large rRNA, arresting protein synthesis at the translocation step. PAP is thought to play an important role in the plant's defense mechanism against foreign pathogens. This review focuses on the structure, function, and the relationship of PAP to other RIPs, discusses molecular aspects of PAP antiviral activity, the novel inhibition of this plant toxin by a virus counteraction-a peptide linked to the viral genome (VPg), and possible applications of RIP-conjugated immunotoxins in cancer therapeutics.