The KNOTTIN database

Knottins are intriguing miniproteins with strong potential in drug design

Welcome to the KNOTTIN database
Database 2011 built from UniProt Knowledgebase Release 2011.8 (see statistics)

News

  • Febryary 2014 :
    The KNOTTIN server is available
      We had to stop the server for technical reasons. It is now available again.
      Please let us know about any trouble you could encounter with this server.
      Also note that we are currently working on the next Database update.
      Thank you for using the KNOTTIN webserver !

  • December 2011 :
    Database update:
     - 34 families, 167 structures, 2193 sequences.

Current Statistics


FamilyCys IVSequences3D Structures
#OrganismsNMRX-RayOrganisms
All families21934501531568
Agouti-related 61 206 104 5 0 2
Alpha-amylase inhibitor 61 1 1 2 1 2
Algae 61 3 1 0 0 0
Bacteria 61 12 7 0 0 0
Bug 61 3 3 2 0 2
Ciliate 61 2 1 0 0 0
Conotoxin1 61 536 60 30 0 8
Conotoxin2 78 6 6 1 0 1
Conotoxin3 77 2 2 0 0 0
Cyclotide 78 192 25 30 1 10
Fungi1 77 67 21 0 0 0
Fungi2 61 51 27 0 0 0
Gurmarin-like 61 1 1 2 0 1
Horseshoe crab 61 5 1 3 0 1
Insect1 61 11 4 1 0 1
Insect2 61 45 22 0 0 0
Maize 78 8 1 0 0 0
Carboxypeptidase inhibitor 77 15 5 2 1 2
Mycetozoa 61 1 1 0 0 0
Plant antimicrobial 61 16 7 1 0 1
Plant defensin 63 4 1 1 0 1
Plant toxin 78 28 17 3 0 3
Plant toxin2 78 0 0 1 0 1
Scorpion1 63 10 9 2 0 1
Scorpion2 61 54 16 4 0 4
Serine protease inhibitor1 78 36 16 10 12 10
Serine protease inhibitor2 61 4 2 0 0 0
Serine protease inhibitor3 61 5 2 0 0 0
Spider 61 775 51 51 0 16
Sponge 61 1 1 0 0 0
Trematoda 61 38 2 0 0 0
Trichoplax 61 1 1 0 0 0
Virus1 61 25 8 2 0 1
Virus2 61 28 23 0 0 0
Water flea 61 1 1 0 0 0

Loop Statistics






What are knottins

Knottins are small disulfide-rich proteins characterized by a very special "disulfide through disulfide knot"

  • 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"


Disulfide connectivity in
Knottins


Disulfide connectivity in
Growth Factor cystine knots


Schematic representation of
Knottins


Schematic representation of
Growth Factor cystine knots


The knottin structural family includes several unrelated families

  • 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.


The knottin fold is an attractive scaffold for drug design

  • 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