Cyclization of pyrrhocoricin retains structural elements crucial for the antimircobial activity of the native peptide

Pyrrhacoricin is a naturally occurring antimicrobial peptide from the European fire bug Pyrrhocoris apterus. It has submicromolar activity against a range of Gram-negative bacterial strains and has created recent interest as a lead for the development of novel antibiotic compounds. In this study, we have used NMR spectroscopy to determine the solution structures of pyrrhocoricin and a synthetic macrocyclic derivative that has improved in vivo pharmaceutical properties. Native pyrrhocoricin is largely disordered in solution, but there is evidence of a subpopulation with ordered turn regions over residues 2-5, 4-7, and 16-19. The macrocyclic derivative incorporates a nine amino acid linker joining the N- and C-termini, which does not adversely affect the antimicrobial potency but leads to a broader spectrum of activity. The NMR data suggest that the turn conformations in the cyclic derivative are similar to those in the native form, thus implicating them in the biological function. (C) 2004 Wiley Periodicals, Inc.

Central elements of the elliptic Zn monodromy matrix algebra at roots of unity

The central elements of the algebra of monodromy matrices associated with the Z(n) R-matrix are studied. When the crossing parameter w takes a special rational value w = n/N, where N and n are positive coprime integers, the center is substantially larger than that in the generic case for which the quantum determinant provides the center. In the trigonometric limit, the situation corresponds to the quantum group at roots of unity. This is a higher rank generalization of the recent results by Belavin and Jimbo. (c) 2004 Elsevier B.V. All rights reserved.

Peptide bundles: Loops, helices, strands and sheets

Protein-protein interactions are central to all biological processes. The creation of small molecules that can structurally mimic the fundamental units of protein architecture (helices, strands, turns, and their combinations) could potentially be used to reproduce important bioactive protein surfaces and interfere in biological processes. Although this field is still in relative infancy, substantial progress is being made in creating small molecules that can mimic these individual secondary structural elements of proteins. However the generation of compounds that can reproduce larger protein surfaces, composed of multiple structural elements of proteins, has proven to be much more challenging. This presentation will describe some densely functionalised small molecules that do constrain multiple peptide motifs in defined structures such as loop bundles, helix bundles, strand and sheet bundles. An example of a helix bundle that undergoes conformational changes to a beta sheet bundle and aggregates into multi-micron length peptide nanofibre 'rope' will be described.

Processing of a 22 kDa precursor protein to produce the circular protein tricyclon A

Cyclotides are a family of plant proteins that have the unusual combination of head-to-tail backbone cyclization and a cystine knot motif. They are exceptionally stable and show resistance to most chemical, physical, and enzymatic treatments. The structure of tricyclon A, a previously unreported cyclotide, is described here. In this structure, a loop that is disordered in other cyclotides forms a beta sheet that protrudes from the globular core. This study indicates that the cyclotide fold is amenable to the introduction of a range of structural elements without affecting the cystine knot core of the protein, which is essential for the stability of the cyclotides. Tricyclon A does not possess a hydrophobic patch, typical of other cyclotides, and has minimal hemolytic activity, making it suitable for pharmaceutical applications. The 22 kDa precursor protein of tricyclon A was identified and provides clues to the processing of these fascinating miniproteins.

Factors influencing the stability of cyclotides: Proteins with a circular backbone and cystine knot motif

Cyclotides are a large family of mini-proteins that have the distinguishing features of a head-to-tail cyclised backbone and a cystine knot formed by six conserved cysteine residues. They are present in plants from the Rubiaceae, Violaceae and Cucurbitaceae families. The unique structural features of the cyclotides make them extremely resistant to chemical, thermal and proteolytic degradation. In this article we review recent Studies from our laboratory that dissect the role of the individual structural elements in defining the stability of cyclotides. The resistance of cyclotides to chemical and proteolytic degradation is in large part due to the cystine knot, whereas the thermal stability is I composite of several features including the cystine knot, the cyclic backbone and the hydrogen bonding network. A range of biological activities of cyclotides is critically dependent oil the presence of the cyclic backbone.