RT Journal Article
T1 Minimized natural versions of fungal ribotoxins show improved active site plasticity
A1 Maestro-López, Moisés
A1 Olombrada, Miriam
A1 García Ortega, Lucía
A1 Serrano González, Daniel
A1 Lacadena, Javier
A1 Oñaderra, Mercedes
A1 Gavilanes, José G.
A1 Martínez del Pozo, Álvaro
AB Fungal ribotoxins are highly specific extracellular RNases which cleave a single phosphodiester bond at the ribosomal sarcin-ricin loop, inhibiting protein biosynthesis by interfering with elongation factors. Most ribotoxins show high degree of conservation, with similar sizes and amino acid sequence identities above 85%. Only two exceptions are known: Hirsutellin A and anisoplin, produced by the entomopathogenic fungi Hirsutella thompsonii and Metarhizium anisopliae, respectively. Both proteins are similar but smaller than the other known ribotoxins (130 vs 150 amino acids), displaying only about 25% sequence identity with them. They can be considered minimized natural versions of their larger counterparts, best represented by α-sarcin. The conserved α-sarcin active site residue Tyr48 has been replaced by the geometrically equivalent Asp, present in the minimized ribotoxins, to produce and characterize the corresponding mutant. As a control, the inverse anisoplin mutant (D43Y) has been also studied. The results show how the smaller versions of ribotoxins represent an optimum compromise among conformational freedom, stability, specificity, and active-site plasticity which allow these toxic proteins to accommodate the characteristic abilities of ribotoxins into a shorter amino acid sequence and more stable structure of intermediate size between that of other nontoxic fungal RNases and previously known larger ribotoxins.
PB Elsevier
SN 1096-0384 (Online)
YR 2017
FD 2017-03-07
LK https://hdl.handle.net/20.500.14352/17687
UL https://hdl.handle.net/20.500.14352/17687
LA eng
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 20 may 2024