PDBsum entry 2jue

Antibiotic, plant protein

PDB id: 2jue

Contents

Protein chain

29 a.a.

PDB id:

2jue

Name:

Antibiotic, plant protein

Title:

Solution structure of the all-d kalata b1

Structure:

Kalata-b1. Chain: a. Fragment: residues 93-121. Engineered: yes

Source:

Synthetic: yes. Synthetic construct. Organism_taxid: 32630. Other_details: d-amino acids

NMR struc:

20 models

Authors:

N.L.Daly,L.Sando,D.Craik

Key ref:

L.Sando et al. (2011). A Synthetic mirror image of kalata B1 reveals that cyclotide activity is independent of a protein receptor. Chembiochem, 12, 2456-2462. PubMed id: 21928440

Date:

23-Aug-07 Release date: 05-Aug-08

Protein chain

P56254  (KAB1_OLDAF) -  Kalata-B1 from Oldenlandia affinis

Chembiochem 12:2456-2462 (2011)

PubMed id: 21928440

A Synthetic mirror image of kalata B1 reveals that cyclotide activity is independent of a protein receptor.

L.Sando, S.T.Henriques, F.Foley, S.M.Simonsen, N.L.Daly, K.N.Hall, K.R.Gustafson, M.I.Aguilar, D.J.Craik.

ABSTRACT

Featuring a circular, knotted structure and diverse bioactivities, cyclotides are a fascinating family of peptides that have inspired applications in drug design. Most likely evolved to protect plants against pests and herbivores, cyclotides also exhibit anti-cancer, anti-HIV, and hemolytic activities. In all of these activities, cell membranes appear to play an important role. However, the question of whether the activity of cyclotides depends on the recognition of chiral receptors or is primarily modulated by the lipid-bilayer environment has remained unknown. To determine the importance of lipid membranes on the activity of the prototypic cyclotide, kalata B1, we synthesized its all-D enantiomer and assessed its bioactivities. After the all-D enantiomer had been confirmed by (1)H NMR to be the structural mirror image of the native kalata B1, it was tested for anti-HIV activity, cytotoxicity, and hemolytic properties. The all-D peptide is active in these assays, albeit with less efficiency; this reveals that kalata B1 does not require chiral recognition to be active. The lower activity than the native peptide correlates with a lower affinity for phospholipid bilayers in model membranes. These results exclude a chiral receptor mechanism and support the idea that interaction with phospholipid membranes plays a role in the activity of kalata B1. In addition, studies with mixtures of L and D enantiomers of kalata B1 suggested that biological activity depends on peptide oligomerization at the membrane surface, which determines affinity for membranes by modulating the association-dissociation equilibrium.