News
- September 2009 :
Database update:
- 30 families, 155 structures, 1621 sequences.
Knottin classification:
- Sequences are classified into families according to Cysteine IV position, origin and/or function.
- - 3 new potential families have been added (Algae, Bacteria, Trichoplax)
- - 2 previous families, Scorpion3 and Terebra, were merged with Scorpion2 and Conotoxin1, respectively.
- - 2 previous families, Insect antimicrobial and Phenoloxidase inhibitor, were renamed as Insect1 and Insect2 respectively.
- June 2008 :
Database update:
- 28 families, 148 structures, 1246 sequences.
- Since they are no more supported by the PDB, theoretical models have been removed.
Cyclic knottins:
- In the standardized alignments, cyclic knottins are now truncated to the postulated
mature peptides.
- This modification is not applied to fragments or linear analogs.
- NB1 Standardized alignments are accessible via: 'Search Database > Selection > Get standardized alignments'.
- NB2 Both the full sequence and the 2D representation (Collier de Perles) of
the putative cyclic mature sequence are available on the individual knottin cards via:
'Search Database (Sequence database) > Green buttons
 '.
- October 2007 :
Structures can be viewed with the Jmol applet:
- Each structure can be displayed using the Jmol link in the 'Structure' tabular outputs.
- Structural superimpositions are available:
1 - Select structures from tabular outputs using checkboxes or the 'Select All' button
2 - choose the "Structural superimposition" radio button
3 - click on the "GET" button
- Knotted cysteines are labeled, and loops are colored as follows:
(a)=green; b=coral; c=aquamarine; (d)=lightblue; e=hotpink
- September 2007 :
The Tool menu has been updated:
- Knoter3d determines if a 3D structure is a knottin.
- Knoter1d predicts if a protein sequence is a knottin.
- Standardized alignments and "Colliers de Perles" are available.
Alignments can now be downloaded as:
- msf, selex, pir or fasta formatted text.
- sequence logo (weblogo).
All knottins in the database (sequences and 3D structures) are renumbered according to
the standard knottin numbering.
- To get standardized alignments use the 'Search Database' menu, then the 'Get alignment' button.
- To get classical pre-compiled alignments use the 'Sequences' menu.
- Sequences or structures can be searched or sorted based on nomenclature (loop lengthes).
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What are knottins
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Knottins are small disulfide-rich proteins
characterized by a very special "disulfide through disulfide knot"
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- This knot is achieved when one disulfide
bridge crosses the macrocycle formed by the two other disulfides
and the interconnecting backbone.
- The knot implies that knottins contain
at least 3 disulfide bridges
- The structural family of knottins have
the disulfide between cysteines III and VI (orange) going through
disulfides I-IV and II-V (yellow).
- The growth factor cystine knots also
contain a knot but the connectivity is different and they cannot
be superimposed onto knottins. These proteins belong to a distinct
structural family not described in this site.
- Knottins are sometime refered to as
"Inhibitor Cystine Knots"
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Disulfide
connectivity in
Knottins
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Disulfide connectivity in
Growth Factor cystine
knots
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Schematic representation of
Knottins
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Schematic representation of
Growth Factor cystine
knots
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The knottin structural family includes several unrelated families
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- Protease inhibitors from plants
- Peptides from the Rubiaceae and the Violaceae plant families
- Toxins from cone snail, spider, bug, horseshoe crab, scorpion
- Gurmarin-like peptides, human Agouti-related protein ...
- Antimicrobial peptides
A number of small disulfide-rich proteins may look like Knottins,
but are not Knottins simply because there is no knot in there
(see a list here).
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The knottin fold is an attractive scaffold for drug design
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- it is small and easily accessible to chemical synthesis
- it is very stable, thanks to the high disulfide content and
the knotted topology
- it is strongly sequence tolerent
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