Kalata B8, a novel antiviral circular protein, exhibits conformational flexibility in the cystine knot motif

Daly, N. L., Clark, R. J., Plan, M. R. and Craik, D. J. (2006) Kalata B8, a novel antiviral circular protein, exhibits conformational flexibility in the cystine knot motif. Biochemical Journal, 393 Part 3: 619-626. doi:10.1042/BJ20051371


Author Daly, N. L.
Clark, R. J.
Plan, M. R.
Craik, D. J.
Title Kalata B8, a novel antiviral circular protein, exhibits conformational flexibility in the cystine knot motif
Journal name Biochemical Journal   Check publisher's open access policy
ISSN 0264-6021
Publication date 2006-01-01
Year available 2006
Sub-type Article (original research)
DOI 10.1042/BJ20051371
Open Access Status Not yet assessed
Volume 393
Issue Part 3
Start page 619
End page 626
Total pages 8
Editor G. Banting
Place of publication London
Publisher Portland Press Ltd
Language eng
Subject C1
250302 Biological and Medical Chemistry
780105 Biological sciences
Abstract The cyclotides are a family of circular proteins with a range of biological activities and potential pharmaceutical and agricultural applications. The biosynthetic mechanism of cyclization is unknown and the discovery of novel sequences may assist in achieving this goal. In the present study, we have isolated a new cyclotide from Oldenlandia affinis, kalata B8, which appears to be a hybrid of the two major subfamilies (Mobius and bracelet) of currently known cyclotides. We have determined the three-dimensional structure of kalata B8 and observed broadening of resonances directly involved in the cystine knot motif, suggesting flexibility in this region despite it being the core structural element of the cyclotides. The cystine knot motif is widespread throughout Nature and inherently stable, making this apparent flexibility a surprising result. Further-more, there appears to be isomerization of the peptide backbone at an Asp-Gly sequence in the region involved in the cyclization process. Interestingly, such isomerization has been previously characterized in related cyclic knottins from Momordica cochinchinensis that have no sequence similarity to kalata B8 apart from the six conserved cysteine residues and may result from a common mechanism of cyclization. Kalata B8 also provides insight into the structure-activity relationships of cyclotides as it displays anti-HIV activity but lacks haemolytic activity. The 'uncoupling' of these two activities has not previously been observed for the cyclotides and may be related to the unusual hydrophilic nature of the peptide.
Keyword Anti-hiv Activity
Cyclic Backbone
Cystine Knot Motif
Haemolytic
Kalata B8
Nmr
Biochemistry & Molecular Biology
Nmr Structure Calculation
Torsion Angle Dynamics
Trypsin-inhibitor
Structural Motif
Plant Cyclotides
Momordica-cochinchinensis
Antimicrobial Peptides
Chassalia-parvifolia
Macrocyclic Peptides
Precursor Protein
Q-Index Code C1
Institutional Status UQ

 
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Created: Wed, 15 Aug 2007, 18:52:41 EST