The cystine knot motif in toxins and implications for drug design

Craik, D. J., Daly, N. L. and Waine, C. (2001) The cystine knot motif in toxins and implications for drug design. Toxicon, 39 1: 43-60. doi:10.1016/S0041-0101(00)00160-4

Author Craik, D. J.
Daly, N. L.
Waine, C.
Title The cystine knot motif in toxins and implications for drug design
Journal name Toxicon   Check publisher's open access policy
ISSN 0041-0101
Publication date 2001-01-01
Year available 2000
Sub-type Article (original research)
DOI 10.1016/S0041-0101(00)00160-4
Open Access Status Not yet assessed
Volume 39
Issue 1
Start page 43
End page 60
Total pages 18
Editor Alan L. Harvey
Place of publication Oxford
Publisher Elsvier Science Ltd
Language eng
Subject C1
250302 Biological and Medical Chemistry
670403 Treatments (e.g. chemicals, antibiotics)
Abstract The cystine knot structural motif is present in peptides and proteins from a variety of species, including fungi, plants, marine molluscs. insects and spiders. It comprises an embedded ring formed by two disulfide bonds and their connecting backbone segments which is threaded by a third disulfide bond. It is invariably associated with nearby beta-sheet structure and appears to be a highly efficient motif for structure stabilization. Because of this stability it makes an ideal framework for molecular engineering applications. In this review we summarize the main structural features of the cystine knot motif, focussing on toxin molecules containing either the inhibitor cystine knot or the cyclic cystine knot. Peptides containing these motifs are 26-48 residues long and include ion channel blockers, haemolytic agents, as well as molecules having antiviral and antibacterial activities. The stability of peptide toxins containing the cystine knot motif, their range of bioactivities and their unique structural scaffold can be harnessed for molecular engineering applications and in drug design. Applications of cystine knot molecules for the treatment of pain. and their potential use in antiviral and antibacterial applications are described. (C) 2000 Elsevier Science Ltd. All rights reserved.
Keyword Pharmacology & Pharmacy
Cyclic Cystine Knot
Knotted Proteins
Inhibitor Cystine Knot
Funnel-web Spider
3-dimensional Solution Structure
Calcium-channel Antagonist
Polypeptide Kalata B1
Omega-conotoxin Gvia
Q-Index Code C1
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 344 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 347 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 15 Aug 2007, 01:43:55 EST