Loop Replacement Enhances the Ancestral Antibacterial Function of a Bifunctional Scorpion Toxin.

ABSTRACT: On the basis of the evolutionary relationship between scorpion toxins targeting K⁺ channels (KTxs) and antibacterial defensins (Zhu S., Peigneur S., Gao B., Umetsu Y., Ohki S., Tytgat J. Experimental conversion of a defensin into a neurotoxin: Implications for origin of toxic function. Mol. Biol. Evol. 2014, 31, 546⁻559), we performed protein engineering experiments to modify a bifunctional KTx (i.e., weak inhibitory activities on both K⁺ channels and bacteria) via substituting its carboxyl loop with the structurally equivalent loop of contemporary defensins. As expected, the engineered peptide (named MeuTXKα3-KFGGI) remarkably improved the antibacterial activity, particularly on some Gram-positive bacteria, including several antibiotic-resistant opportunistic pathogens. Compared with the

SUBMITTER: Zhang S 

PROVIDER: S-EPMC6024585 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature