Knottins proteins are a new division of small disulfide-rich proteins characterized by a very special “disulfide through disulfide knot” in a classification of proteins.
This knot is achieved when one disulfide bridge crosses the macrocycle formed by the two other disulfides and the interconnecting backbone.
The knot structure implies that knottins contain at least 3 disulfide bridges in protein structure
Understanding better structural family of knottins proteins, they 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.