The cyclotides are a large family of circular mini-proteins containing a cystine knot motif. They are expressed in plants as defense-related proteins, with insecticidal activity. Here we investigate their role in membrane interaction and disruption. Kalata B1, a prototypic cyclotide, was found to induce leakage of the self-quenching fluorophore, carboxyfluorescein, from phospholipid vesicles. A...

In recent years an increasing number of miniproteins containing an amide-cyclized backbone have been discovered. The cyclotide family is the largest group of such proteins and is characterized by a circular protein backbone and six conserved cysteine residues linked by disulfide bonds in a tight core of the molecule. These form a cystine knot in which an embedded ring formed by two of the disul...

We have determined the three-dimensional structure of a two-disulfide intermediate (Cys(8)-Cys(20), Cys(14)-Cys(26)) on the oxidative folding pathway of the cyclotide MCoTI-II. Cyclotides have a range of bioactivities and, because of their exceptional stability, have been proposed as potential molecular scaffolds for drug design applications. The three-dimensional structure of the stable two-di...

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) and is characterized by the destruction of myelin and axons leading to progressive disability. Peptide epitopes from CNS proteins, such as myelin oligodendrocyte glycoprotein (MOG), possess promising immunoregulatory potential for treating MS; however, their instability and poor bioavailability is a major imp...

Kalata B1 (kB1), a cyclotide that has been used in medical applications, displays cytotoxicity related to membrane binding and oligomerization. Our molecular dynamics simulation results demonstrate that Trp19 in loop 5 of both monomeric and tetrameric kB1 is a key residue for initial anchoring in the membrane binding process. This residue also facilitates the formation of kB1 tetramers. Additio...

The genus Viola (Violaceae) consists of approximately 500 species widely distributed throughout the world. In Pakistan, seventeen (17) different species of viola are abundantly found. Traditional healers have been patronizing various species of this genus in numerous disorders since time immemorial. Some of them are already validated scientifically such as antifungal antibacterial, antiplasmodi...