2fqa
From Proteopedia
(New page: 200px<br /><applet load="2fqa" size="450" color="white" frame="true" align="right" spinBox="true" caption="2fqa" /> '''Violacin A'''<br /> ==Overview== Cyclotides...) |
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| - | [[Image:2fqa.jpg|left|200px]]<br /><applet load="2fqa" size=" | + | [[Image:2fqa.jpg|left|200px]]<br /><applet load="2fqa" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2fqa" /> | caption="2fqa" /> | ||
'''Violacin A'''<br /> | '''Violacin A'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Cyclotides are mini-proteins of 28-37 amino acid residues that have the | + | Cyclotides are mini-proteins of 28-37 amino acid residues that have the unusual feature of a head-to-tail cyclic backbone surrounding a cystine knot. This molecular architecture gives the cyclotides heightened resistance to thermal, chemical and enzymatic degradation and has prompted investigations into their use as scaffolds in peptide therapeutics. There are now more than 80 reported cyclotide sequences from plants in the families Rubiaceae, Violaceae and Cucurbitaceae, with a wide variety of biological activities observed. However, potentially limiting the development of cyclotide-based therapeutics is a lack of understanding of the mechanism by which these peptides are cyclized in vivo. Until now, no linear versions of cyclotides have been reported, limiting our understanding of the cyclization mechanism. This study reports the discovery of a naturally occurring linear cyclotide, violacin A, from the plant Viola odorata and discusses the implications for in vivo cyclization of peptides. The elucidation of the cDNA clone of violacin A revealed a point mutation that introduces a stop codon, which inhibits the translation of a key Asn residue that is thought to be required for cyclization. The three-dimensional solution structure of violacin A was determined and found to adopt the cystine knot fold of native cyclotides. Enzymatic stability assays on violacin A indicate that despite an increase in the flexibility of the structure relative to cyclic counterparts, the cystine knot preserves the overall stability of the molecule. |
==About this Structure== | ==About this Structure== | ||
| - | 2FQA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Viola_odorata Viola odorata]. Full crystallographic information is available from [http:// | + | 2FQA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Viola_odorata Viola odorata]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FQA OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Viola odorata]] | [[Category: Viola odorata]] | ||
| - | [[Category: Craik, D | + | [[Category: Craik, D J.]] |
| - | [[Category: Daly, N | + | [[Category: Daly, N L.]] |
| - | [[Category: Ireland, D | + | [[Category: Ireland, D C.]] |
[[Category: beta sheet]] | [[Category: beta sheet]] | ||
[[Category: beta turns]] | [[Category: beta turns]] | ||
[[Category: cystine knot]] | [[Category: cystine knot]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:24:06 2008'' |
Revision as of 15:24, 21 February 2008
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Violacin A
Overview
Cyclotides are mini-proteins of 28-37 amino acid residues that have the unusual feature of a head-to-tail cyclic backbone surrounding a cystine knot. This molecular architecture gives the cyclotides heightened resistance to thermal, chemical and enzymatic degradation and has prompted investigations into their use as scaffolds in peptide therapeutics. There are now more than 80 reported cyclotide sequences from plants in the families Rubiaceae, Violaceae and Cucurbitaceae, with a wide variety of biological activities observed. However, potentially limiting the development of cyclotide-based therapeutics is a lack of understanding of the mechanism by which these peptides are cyclized in vivo. Until now, no linear versions of cyclotides have been reported, limiting our understanding of the cyclization mechanism. This study reports the discovery of a naturally occurring linear cyclotide, violacin A, from the plant Viola odorata and discusses the implications for in vivo cyclization of peptides. The elucidation of the cDNA clone of violacin A revealed a point mutation that introduces a stop codon, which inhibits the translation of a key Asn residue that is thought to be required for cyclization. The three-dimensional solution structure of violacin A was determined and found to adopt the cystine knot fold of native cyclotides. Enzymatic stability assays on violacin A indicate that despite an increase in the flexibility of the structure relative to cyclic counterparts, the cystine knot preserves the overall stability of the molecule.
About this Structure
2FQA is a Single protein structure of sequence from Viola odorata. Full crystallographic information is available from OCA.
Reference
Discovery and characterization of a linear cyclotide from Viola odorata: implications for the processing of circular proteins., Ireland DC, Colgrave ML, Nguyencong P, Daly NL, Craik DJ, J Mol Biol. 2006 Apr 14;357(5):1522-35. Epub 2006 Feb 2. PMID:16488428
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