title: The PDB database is a rich source of alpha-helical anti-microbial peptides to combat disease causing pathogens.
abstract: The therapeutic potential of α-helical anti-microbial peptides (AH-AMP) to combat pathogens is fast gaining prominence. Based on recently published open access software for characterizing α-helical peptides (PAGAL), we elucidate a search methodology (SCALPEL) that leverages the massive structural data pre-existing in the PDB database to obtain AH-AMPs belonging to the host proteome. We provide in vitro validation of SCALPEL on plant pathogens ( Xylella fastidiosa, Xanthomonas arboricola and Liberibacter crescens) by identifying AH-AMPs that mirror the function and properties of cecropin B, a well-studied AH-AMP. The identified peptides include a linear AH-AMP present within the existing structure of phosphoenolpyruvate carboxylase (PPC20), and an AH-AMP mimicing the properties of the two α-helices of cecropin B from chitinase (CHITI25). The minimum inhibitory concentration of these peptides are comparable to that of cecropin B, while anionic peptides used as control failed to show any inhibitory effect on these pathogens. Substitute therapies in place of conventional chemotherapies using membrane permeabilizing peptides like these might also prove effective to target cancer cells. The use of native structures from the same organism could possibly ensure that administration of such peptides will be better tolerated and not elicit an adverse immune response. We suggest a similar approach to target Ebola epitopes, enumerated using PAGAL recently, by selecting suitable peptides from the human proteome, especially in wake of recent reports of cationic amphiphiles inhibiting virus entry and infection.
authors.affiliation: Plant Sciences Department, University of California, Davis, CA, 95616, USA; Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai, 400 005, India.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Chakraborty
authors.affiliation: Plant Sciences Department, University of California, Davis, CA, 95616, USA.
authors.forename: My
authors.initials: M
authors.lastname: Phu
authors.affiliation: Institute of Agricultural Sciences, Federal University of Uberlandia, Av. Amazonas, Bloco 2E, Campus Umuarama, Uberlandia, MG, Brazil.
authors.forename: Tâmara Prado
authors.initials: TP
authors.lastname: de Morais
authors.affiliation: Institute of Genetics and Biochemistry, Federal University of Uberlandia, Av. Amazonas, Bloco 2E, Campus Umuarama, Uberlandia, MG, Brazil.
authors.forename: Rafael
authors.initials: R
authors.lastname: Nascimento
authors.affiliation: Institute of Genetics and Biochemistry, Federal University of Uberlandia, Av. Amazonas, Bloco 2E, Campus Umuarama, Uberlandia, MG, Brazil.
authors.forename: Luiz Ricardo
authors.initials: LR
authors.lastname: Goulart
authors.affiliation: Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai, 400 005, India.
authors.forename: Basuthkar J
authors.initials: BJ
authors.lastname: Rao
authors.affiliation: Science Institute, Department of Biochemistry, University of Iceland, Dunhaga 3, IS-107 Reykjavik, Iceland.
authors.forename: Bjarni
authors.initials: B
authors.lastname: Asgeirsson
authors.affiliation: Plant Sciences Department, University of California, Davis, CA, 95616, USA.
authors.forename: Abhaya M
authors.initials: AM
authors.lastname: Dandekar
keywords: Ebola; PDB database; SCALPEL; alpha-helical antimicrobial peptides
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