2IGR

Solution structure of CB1a, a novel anticancer peptide derived from natural antimicrobial peptide cecropin B

Summary for 2IGR

• Entry DOI: 10.2210/pdb2igr/pdb
• Related: 1D9J 1D9M 1D9O 1D9P
• Descriptor: Anticancer peptide CB1a (1 entity in total)
• Functional Keywords: anticancer peptide, cecropin, antimicrobial peptide, ploycationic peptide, cecropin fingerprint sequence, de novo protein, lipid binding protein
• Biological source: Hyalophora cecropia (Cecropia moth)
• Total number of polymer chains: 1
• Total formula weight: 4203.32

Authors

Wu, J.-M. (deposition date: 2006-09-24, release date: 2006-11-18, Last modification date: 2024-10-30)

Primary citation

Wu, J.-M.,Jan, P.-S.,Yu, H.-C.,Haung, H.-Y.,Fang, H.-J.,Chang, Y.-I.,Cheng, J.-W.,Chen, H.M.
Structure and function of a custom anticancer peptide, CB1a
Peptides, 30:839-848, 2009

PubMed Abstract: Several natural antimicrobial peptides including cecropins, magainins and melittins have been found to kill cancer cells. However, their efficacy may not be adequate for their development as anticancer agents. In this study, we used a natural antimicrobial peptide, cecropin B (CB), as a template to generate a novel anticancer peptide. Cecropin B is an amphipathic and polycationic peptide derived from the hemolymph of Hyalophora cecropia with well-known antimicrobial and cytolytic properties. The signature pattern of cecropins is W-x-(0,2)-[KDN]-x-{L}-K-[KRE]-[LI]-E-[RKN] (PROSITE: PS00268), and this signature sequence is located at N-terminus of CB. CB1a was constructed by repeating the N-terminal ten amino acids of CB three times and including a hinge near C-terminus. The circular dichroism spectra showed that CB1a is unstructured in aqueous solution, but adopt a helical conformation in membrane-like environment. The solution structure of CB1a in a polar solvent was also studied by NMR. CB1a formed a helix-hinge-helix in 20% HFIP solution, and it was found the bent angle between two helical segments was induced ranging from 60 degrees to 110 degrees . A heparin-binding motif is located in the central part of helix 1. Isothermal titration calorimetry reveals the association constant of CB1a bound to low molecular weight heparin is 1.66 x 10(5)M(-1) at physiological ionic strength at 25 degrees C. Binding of CB1a to heparin produces a large conformational change toward a more structural state. CB1a demonstrated promising activity against several cancer cells but low toxicity against non-cancer cells. The IC(50) of CB1a on leukemia and stomach carcinoma cells were in the range of 2-8-fold lower than those of CB. Besides, CB1a exhibited low hemolytic activity against human red blood cells. Due to these properties, CB1a has the potential to become a promising anticancer agent.

PubMed: 19428759
DOI: 10.1016/j.peptides.2009.02.004

Experimental method

SOLUTION NMR