Welcome to the KNOTTIN database

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 (blue) going through disulfides I-IV and II-V (green).

• 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".

‣ 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 proteins

• 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, since it is

• Small and easily accessible to chemical synthesis,

• Very stable, thanks to the high disulfide content and the knotted topology,

• Strongly sequence tolerent.