Asparaginyl endopeptidases (AEPs) are versatile enzymes that in biological systems are involved in producing three different catalytic outcomes for proteins, namely (i) routine cleavage by bond hydrolysis, (ii) peptide maturation, including macrocyclisation by a cleavage-coupled intramolecular transpeptidation and (iii) circular permutation involving separate cleavage and transpeptidation reactions resulting in a major reshuffling of protein sequence. (silverchair.com)
Cysteine2
The six cysteine residues are absolutely conserved throughout the cyclotide suite and presumably contribute to preserving the CCK motif. (wikipedia.org)
Cyclotides are plant peptides characterized with a head-to-tail cyclized backbone and three interlocking disulfide bonds, known as a cyclic cysteine knot. (bvsalud.org)
Head-to-tail2
Typically containing 28-37 amino acids, they are characterized by their head-to-tail cyclised peptide backbone and the interlocking arrangement of their three disulfide bonds. (wikipedia.org)
We demonstrate the effectiveness of this approach by identifying drug-like, head-to-tail cyclic peptides that modulate the aggregation of the Alzheimer's disease-associated amyloid β peptide. (nature.com)
Sequence3
The amino acid sequence (single-letter amino acid representation) for this peptide is indicated on the sequence diagram to the right. (wikipedia.org)
Analysis of the suite of known cyclotides reveals many sequence similarities that are important for understanding their unique physico-chemical properties, bioactivities and homology. (wikipedia.org)
This structure is similar to kalata B1 and circulin A, the only two macrocyclic peptides for which a structure was available, suggesting that despite the sequence variation throughout the peptides they form a family in which the overall fold is conserved. (rcsb.org)
Trypsin1
A third subfamily of cyclotides are trypsin inhibitors and are more homologous to a family of non-cyclic trypsin inhibitors from squash plants known as knottins or inhibitor cystine knots than they are to the other cyclotides. (wikipedia.org)
Kalata2
In the case of kalata B1 the indicated glycine (G) and asparagine (N) amino acids are the terminal residues that are linked in a peptide bond to cyclize the peptide. (wikipedia.org)
The potent insecticidal activity of cyclotides kalata B1 and kalata B2 has prompted the belief that cyclotides act as plant host-defence agents. (wikipedia.org)
Bioactivities1
Cyclotides also display bioactivities that have been exploited and expanded to develop as potential therapeutic reagents for a wide range of conditions (e.g. (bvsalud.org)
Amino acid1
Peptides whose amino acid residues are linked together forming a circular chain. (bvsalud.org)
Oldenlandia1
We have significantly expanded the range of known macrocyclic peptides with the discovery of 16 novel peptides from extracts of Viola hederaceae, Viola odorata and Oldenlandia affinis. (rcsb.org)
Cyclic cystine knot1
We refer to these peptides as the cyclotide family and their embedded topology as the cyclic cystine knot (CCK) motif. (rcsb.org)
To date, over 100 cyclotides have been isolated and characterized from species of the families Rubiaceae, Violaceae, and Cucurbitaceae. (wikipedia.org)
Sequences2
With recent screening programs suggesting that the number of cyclotide sequences may soon reach the thousands, a database, CyBase, has been developed that offers the opportunity for comparisons of sequences and activity data for cyclotides. (wikipedia.org)
Despite the variations in cyclotides peptide sequences, this core structure is conserved, underlying their most useful feature: stability against thermal and chemical breakdown. (bvsalud.org)
Backbone3
Cyclotides have a well-defined three-dimensional structure due to their interlocking disulfide bonds and cyclic peptide backbone. (wikipedia.org)
Moebius cyclotides, the less common of the two, contain a cis-proline in loop 5 that induces a local 180° backbone twist (hence likening it to a Möbius strip), whereas bracelet cyclotides do not. (wikipedia.org)
The second subfamily contains a backbone twist due to a cis-Pro peptide bond and may conceptually be regarded as a molecular Moebius strip. (rcsb.org)
Structures1
DSC thermogram showed that the cyclotide nanotubes were stable after heating until 200 °C. Fluorescence microscopy images proved that the self-assembled structures of cyclotide can encapsulate the coumarin. (bvsalud.org)
Biological5
Several macrocyclic peptides ( approximately 30 amino acids), with diverse biological activities, have been isolated from the Rubiaceae and Violaceae plant families over recent years. (rcsb.org)
Cyclotides, or cyclic peptides used by some plant families as defense agents, have attracted the interest of scientists because of their biological activities varying from antimicrobial to anticancer properties. (bvsalud.org)
These results suggested that the cyclotide nanotubes could be considered as a new carrier in biological fields while they are biocompatible. (bvsalud.org)
Biochemical, biophysical and biological assays using isolated amyloid β peptide, primary neurons and various established Alzheimer's disease nematode models showed that the selected macrocycles potently inhibit the formation of neurotoxic amyloid β peptide aggregates. (nature.com)
His research integrates issues of Cyclic peptide, Biological activity, Pharmacognosy and Sponge in his study of Stereochemistry. (research.com)
Species1
The Viola plants had not previously been examined for these peptides and thus represent novel species in which these unusual macrocyclic peptides are produced. (rcsb.org)
Residues3
Although the cysteines appear essential to maintaining the overall fold, several other residues highly conserved in cyclotides are thought to provide additional stability. (wikipedia.org)
This loop is believed to play an important role in stabilizing the cyclotide structure through hydrogen bonding with residues from loops 3 and 5. (wikipedia.org)
Other conserved residues include a hydroxyl-containing residue in loop 3, a glycine residue in the final position of loop 3, a basic and a proline residue in the penultimate position in loop 5 of bracelet and Möbius cyclotides respectively, and an asparagine (or occasionally aspartic acid) residue at the putative cyclisation point in loop 6. (wikipedia.org)
Here we define the structural features of the two apparent subfamilies of the CCK peptides which may be significant for the likely defense related role of these peptides within plants. (rcsb.org)
Viola1
Cyclotide extract was obtained from Viola ignobilis by a low voltage electric field extraction method and characterized by HPLC and matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF). (bvsalud.org)
Plant3
The observations that dozens or more cyclotides may be present in a single plant and the cyclotide architecture comprises a conserved core onto which a series of hypervariable loops is displayed suggest that cyclotides may be able to target many pests/pathogens simultaneously. (wikipedia.org)
Transpeptidation by plant AEPs is often intramolecular, in that the free N-terminal nucleophile originates from the same molecule in which the initial cleavage reaction occurs, resulting in peptide macrocyclisation. (silverchair.com)
Ribosomally synthesized homodetic plant cyclic peptides that have N-to-C amide bonds rather than disulfide bonds. (bvsalud.org)
Bonds1
The discovery of butelase-1, an extremely efficient AEP (catalytic efficiency of up to 1 340 000 M −1 s −1 on a non-native substrate) [ 6 , 7 ] that forms peptide bonds via a cleavage-coupled transpeptidation reaction, has led to a surge of interest in AEPs. (silverchair.com)
Stability1
The stability of cyclotide nanotubes after 3 months of keeping at -20 °C was determined by field emission scanning electron microscopy (FESEM). (bvsalud.org)
Structure2
Further, we have determined the three-dimensional structure of one of these novel peptides, cycloviolacin O1, using (1)H NMR spectroscopy. (rcsb.org)
As such, in vitro production of cyclotides is of the utmost importance since it could assist further research on this peptide class, specifically the structure-activity relationship and its mechanism of action. (bvsalud.org)
Families1
Cyclotides have also been identified in agriculturally important families such as the Fabaceae and Poaceae. (wikipedia.org)
Simultaneously1
In this system, large combinatorial libraries of macrocyclic molecules are biosynthesized in Escherichia coli cells and simultaneously screened for their ability to rescue pathogenic protein misfolding and aggregation using a flow cytometric assay. (nature.com)
Discovery2
These findings demonstrate that the use of microfluidic channels has a high impact on the separation of cyclotides as a rapid, cost-effective, and simple method and the device can find widespread applications in drug discovery research. (bvsalud.org)
Fig. 1: High-throughput genetic screening for the discovery of macrocyclic rescuers of pathogenic Aβ misfolding and aggregation. (nature.com)
Class1
Cyclotides are a class of cyclic peptides that can be self-assembled. (bvsalud.org)
Plants1
Plants are a rich source of ribosomally-synthesised and post-translationally modified cyclic peptides. (wikipedia.org)
Properties1
This study aimed to discover the properties of cyclotide nanotubes. (bvsalud.org)
Terms1
The separation process has a critical impact in terms of obtaining pure cyclotides for drug development strategies. (bvsalud.org)
Cells1
The cytocompatibility of cyclotide nanotubes was evaluated on peripheral blood mononuclear cells. (bvsalud.org)