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Evidence for the importance of electrostatics in the function of two distinct families of ribosome inactivating toxins.
RNA. 2007 Sep; 13(9):1391-6.RNA

Abstract

Alpha-sarcin and ricin represent two structurally and mechanistically distinct families of site-specific enzymes that block translation by irreversibly modifying the sarcin/ricin loop (SRL) of 23S-28S rRNA. alpha-Sarcin family enzymes are designated as ribotoxins and act as endonucleases. Ricin family enzymes are designated as ribosome inactivating proteins (RIP) and act as N-glycosidases. Recently, we demonstrated that basic surface residues of the ribotoxin restrictocin promote rapid and specific ribosome targeting by this endonuclease. Here, we report that three RIP: ricin A, saporin, and gypsophilin depurinate the ribosome with strong salt sensitivity and achieve unusually fast kcat/Km approximately 10(9)-10(10) M(-1) s(-1), implying that RIP share with ribotoxins a common mechanism of electrostatically facilitated ribosome targeting. Bioinformatics analysis of RIP revealed that surface charge properties correlate with the presence of the transport chain in the RIP molecule, suggesting a second role for the surface charge in RIP transport. These findings put forward surface electrostatics as an important determinant of RIP activity.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Letter
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17626843

Citation

Korennykh, Alexei V., et al. "Evidence for the Importance of Electrostatics in the Function of Two Distinct Families of Ribosome Inactivating Toxins." RNA (New York, N.Y.), vol. 13, no. 9, 2007, pp. 1391-6.
Korennykh AV, Correll CC, Piccirilli JA. Evidence for the importance of electrostatics in the function of two distinct families of ribosome inactivating toxins. RNA. 2007;13(9):1391-6.
Korennykh, A. V., Correll, C. C., & Piccirilli, J. A. (2007). Evidence for the importance of electrostatics in the function of two distinct families of ribosome inactivating toxins. RNA (New York, N.Y.), 13(9), 1391-6.
Korennykh AV, Correll CC, Piccirilli JA. Evidence for the Importance of Electrostatics in the Function of Two Distinct Families of Ribosome Inactivating Toxins. RNA. 2007;13(9):1391-6. PubMed PMID: 17626843.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence for the importance of electrostatics in the function of two distinct families of ribosome inactivating toxins. AU - Korennykh,Alexei V, AU - Correll,Carl C, AU - Piccirilli,Joseph A, Y1 - 2007/07/12/ PY - 2007/7/14/pubmed PY - 2007/10/18/medline PY - 2007/7/14/entrez SP - 1391 EP - 6 JF - RNA (New York, N.Y.) JO - RNA VL - 13 IS - 9 N2 - Alpha-sarcin and ricin represent two structurally and mechanistically distinct families of site-specific enzymes that block translation by irreversibly modifying the sarcin/ricin loop (SRL) of 23S-28S rRNA. alpha-Sarcin family enzymes are designated as ribotoxins and act as endonucleases. Ricin family enzymes are designated as ribosome inactivating proteins (RIP) and act as N-glycosidases. Recently, we demonstrated that basic surface residues of the ribotoxin restrictocin promote rapid and specific ribosome targeting by this endonuclease. Here, we report that three RIP: ricin A, saporin, and gypsophilin depurinate the ribosome with strong salt sensitivity and achieve unusually fast kcat/Km approximately 10(9)-10(10) M(-1) s(-1), implying that RIP share with ribotoxins a common mechanism of electrostatically facilitated ribosome targeting. Bioinformatics analysis of RIP revealed that surface charge properties correlate with the presence of the transport chain in the RIP molecule, suggesting a second role for the surface charge in RIP transport. These findings put forward surface electrostatics as an important determinant of RIP activity. SN - 1355-8382 UR - https://www.unboundmedicine.com/medline/citation/17626843/Evidence_for_the_importance_of_electrostatics_in_the_function_of_two_distinct_families_of_ribosome_inactivating_toxins_ L2 - http://www.rnajournal.org/cgi/pmidlookup?view=long&pmid=17626843 DB - PRIME DP - Unbound Medicine ER -