STRUCTURAL FEATURES OF StAsp-PSIr AND SAPLIPs COULD EXPLAIN CYTOTOXIC SELECTIVITY

MUÑOZ, FF; DALEO, GR AND GUEVARA, MG

Villa Carlos Paz, Córdoba, Argentina.

Congreso; Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2008

We have reported the antimicrobial activity of a domain present in potato aspartic proteases, called plant-specific insert (StAsp-PSI). This domain has a high structural homology with Saposin-like proteins (SAPLIPs) with antimicrobial/antitumoral activities. The aim of this work was to analyse if similarities/differences between StAsp-PSIr and SAPLIPs, found in the cytotoxic activities, can be explained by similar/different 3-D structures. Comparisons of NK-Lysin, Granulysin and SP-B with StAsp-PSIr model showed that antibacterial activity towards E. coli and B. cereus would be dependent on the helix 1-helix 5 structure; while the hydrolytic activity towards S. aureus, only present in SP-B and StAsp-PSIr, would be influenced by residues L97, C98 and A100 in the helix 4 which are similar to SP-B. In addition, we have identified residues in the helix 4 (K113, K118, K120) that may account for the antimicrobial activity against Gram- bacteria, as reported for SP-B. The motive of SP-B which is responsible for bacterial aggregation showed that helices 4 and 5 would be related with this activity previously reported for StAPs. The analysis performed here suggests that SIMILARITIES AND DIFFERENCES IN THE STRUCTURAL FEATURES BETWEEN StAsp-PSIr AND SAPLIPs COULD EXPLAIN CYTOTOXIC SELECTIVITY. However, mutagenesis assays will be necessary to corroborate this hypothesis.