1.C.124.  The Antimicrobial Pore-forming Pandinin (Pin) Family 

Pandinin 2 (Pin2) is a pore-forming α-helical polycationic peptide from the venom of the African scorpion, Pandinus imperator, with high antimicrobial activity against Gram-positive bacteria but less active against Gram-negative bacteria (Nomura et al. 2004, Belokoneva et al. 2004).  However it has strong hemolytic activity against sheep red blood cells. In the chemically synthesized Pin2GVG analog, the GVG motif minimizes its hemolytic activity while maintaining its antimicrobial activity (Velasco-Bolom et al. 2017).

The membrane disruption mechanism of the antimicrobial peptide from the venom of the African scorpion, pandinin 1 (pin1) has been studied, showing that the two α-helical regions move around the central hinge region, which contains Pro19. 31P NMR spectra of lipid membranes in the presence of pin1, at various temperatures, showed that pin1 induces various lipid phase behaviors depending on the acyl chain length and charge of phospholipids.  pin1 is located at the membrane-water interface approximately parallel to the bilayer surface. Solid-state NMR results correlated well with the observed biological activity of pin1 in red blood cells and bacteria (Nomura et al. 2005).


This family belongs to the Cecropin Superfamily.
 

References:

Belokoneva, O.S., H. Satake, E.L. Mal'tseva, N.P. Pal'mina, E. Villegas, T. Nakajima, and G. Corzo. (2004). Pore formation of phospholipid membranes by the action of two hemolytic arachnid peptides of different size. Biochim. Biophys. Acta. 1664: 182-188.
Nomura, K., G. Corzo, T. Nakajima, and T. Iwashita. (2004). Orientation and pore-forming mechanism of a scorpion pore-forming peptide bound to magnetically oriented lipid bilayers. Biophys. J. 87: 2497-2507.
Nomura, K., G. Ferrat, T. Nakajima, H. Darbon, T. Iwashita, and G. Corzo. (2005). Induction of morphological changes in model lipid membranes and the mechanism of membrane disruption by a large scorpion-derived pore-forming peptide. Biophys. J. 89: 4067-4080.
Orivel, J., V. Redeker, J.P. Le Caer, F. Krier, A.M. Revol-Junelles, A. Longeon, A. Chaffotte, A. Dejean, and J. Rossier. (2001). Ponericins, new antibacterial and insecticidal peptides from the venom of the ant Pachycondyla goeldii. J. Biol. Chem. 276: 17823-17829.
Rodríguez, A., E. Villegas, A. Montoya-Rosales, B. Rivas-Santiago, and G. Corzo. (2014). Characterization of antibacterial and hemolytic activity of synthetic pandinin 2 variants and their inhibition against Mycobacterium tuberculosis. PLoS One 9: e101742.
Velasco-Bolom, J.L., G. Corzo, and R. Garduño-Juárez. (2017). Molecular dynamics simulation of the membrane binding and disruption mechanisms by antimicrobial scorpion venom-derived peptides. J Biomol Struct Dyn 1-15. [Epub: Ahead of Print]
Wu, S., Y. Nie, X.C. Zeng, H. Cao, L. Zhang, L. Zhou, Y. Yang, X. Luo, and Y. Liu. (2014). Genomic and functional characterization of three new venom peptides from the scorpion Heterometrus spinifer. Peptides 53: 30-41.
Examples:

TC#NameOrganismal TypeExample
1.C.124.1.1

Pandinin2 of 24 aas and 1 TMS.  Forms pores and disrupts membranes of bacteria and fungi (Rodríguez et al. 2014).

Pandinin-2 of Pandinus imperator

 
1.C.124.1.2

Heterin-1 of 43 aas and 1 TMS.  Heterin-1 possesses potent activities against both Gram-positive and Gram-negative bacteria. Among the tested bacterial species, Heterin-1 is the most active against Bacillus megaterium and Micrococcus luteus with MICs of 4.0 μM for both (Wu et al. 2014).

Heterin-1 of Heterometrus spinifer (Asia giant forest scorpion) (Malaysian black scorpion)

 
1.C.124.1.3

Venom toxin of 73 aas and 1 TMS.

Venom toxin of Hemiscorpius lepturus (scorpion)

 
1.C.124.1.4

Scorpion toxin, OcyC3, of 75 aas and 1 TMS. Also called antimicrobial peptide NDBP 4.1.

OcyC3 of Opisthacanthus cayaporum (South American scorpion)

 
1.C.124.1.5

Ponericin-W5 of 24 aas and 1 TMS. Has a broad spectrum of activities against both Gram-positive and Gram-negative bacteria as well as Saccharomyces cerevisiae. It also has insecticidal and hemolytic activities (Orivel et al. 2001).

Ponericin-W5 of Pachycondyla goeldii (Ponerine ant)

 
Examples:

TC#NameOrganismal TypeExample
1.C.124.2.1

Pandinin 1, Pin1, of 44 aas and 0 TMS.  Pin1 is located at the membrane-water interface, approximately parallel to the bilayer surface. Solid-state NMR results correlated well with the observed biological activity of pin1 in red blood cells and bacteria (Nomura et al. 2005). Pin-1 and Pin-2 are not demonstrably homologous.

Pin-1 of Pandinus imperator