The KNOTTIN website and database: a new information system dedicated to the knottin scaffold

Abstract

The KNOTTIN website and database organize information about knottins or inhibitor cystine knots, small disulfide-rich proteins with a knotted topology. Thanks to their small size and high stability, knottins provide appealing scaffolds for protein engineering and drug design. Static pages present the main historical and recent results about knottin discoveries, sequences, structures, folding, functions, applications and bibliography. Database searches provide dynamically generated tabular reports or sequence alignments for knottin three-dimensional structures or sequences. BLAST/HMM searches are also available. A simple nomenclature, based on loop lengths between cysteines, is proposed and is complemented by a uniform numbering scheme. This standardization is applied to all knottin structures in the database, facilitating comparisons. Renumbered and structurally fitted knottin PDB files are available for download. The standardized numbering is used for automatic drawing of two-dimensional Colliers de Perles. The KNOTTIN website and database are available at http://knottin.cbs.cnrs.fr and http://knottin.com.

A Continent of Plant Defense Peptide Diversity: Cyclotides in AustralianHybanthus(Violaceae)

“…Initiatives in collating this emerging information have been made for knottins (Gelly et al, 2004) and antimicrobial peptides (Tossi and Sandri, 2002;Brahmachary et al, 2004;Wang and Wang, 2004) in the form of online databases of the expanding list of cDNA and peptide sequences and their structures and activities. A database of cyclotide sequences (www.cyclotide.com) will soon be substantially updated to accommodate this rapidly growing family.…”

Structures of the Agouti Signaling Protein

“…Cystine knots are ubiquitous and fall into two classes: growth factor cystine knots and inhibitor cystine knots (ICK), 25,26 the latter of which are often referred to as knottins. 27 The defining feature of the general cystine knot fold is a topological circle formed by two disulfide bonds, and their interconnecting peptide segments, threaded by a third disulfide. The two fold classes are distinguished by the specific disulfide that threads the topological circle, which in the ICK motif involves the third cysteine.…”

Molecular diversity and evolution of cystine knot toxins of the tarantula Chilobrachys jingzhao

“…The signal peptides were predicted with the SignalP 3.0 program (http://www.cbs.dtu.dk/services/SignalP/). Furthermore, the putative CKTs were searched in KNOTTIN database (http://knottin.cbs.cnrs.fr) [10,21]. Multiple sequences of precursors were aligned using the ClustalW program [22,23].…”

“…The properties and structures of toxins from spider venoms have been reviewed in detail [3, 5 -7]. Tarantulas use two major scaffolds as templates to develop their "pharmaceutical factory", namely the inhibitor cystine knot (ICK) [8,9], which is also referred to as knottin [10], and less prominently, the disulfidedirected b-hairpin (DDH)-derived fold [11,12]. However, the classification and evolution of tarantula CKTs remain uncertain [13], possibly due to lack of sequence data, especially full-length cDNA information.…”