Kalicludine

"Kali", abbreviated from the Latin word "kalium", equals potassium. "Cludine" means to block or to enclose, as it is derived from the Latin verb "cludere".

Kalicludine (uniprot ID: Q9TWG0) is also known as KappaPI-actitoxin-Avd3b or as Kunitz-type serine protease inhibitor kalicludine-1.^[1] Thus, kalicludines are part of the Kunitz-type inhibitor superfamily. The Kunitz-type scaffold is found both in inhibitors of proteolytic enzymes and in toxins.^[2] Other members of this superfamily are the pancreatic trypsin inhibitors (BPTI), which are potent Kunitz-type protease inhibitors, and dendrotoxins. Kalicludine has 40% homology with BPTIs.^[3] The most represented sequences of this group corresponds with kalicludine-3 and kalicludine-4, a recently found polypeptide.

A. sulcata kalicludines include AsKC1, AsKC2, and AsKC3.,^[4] which are related to Bunodosoma granulifera toxin k (BgK) and Stichodactyla helianthus toxin k (ShK).^[3] A different, less abundant, protein is AsKC1a, which has a supplementary residue at the C-terminus when compared with kalicludine-1. Furthermore, a level of amino acid sequence identity and similarity of ≥43% and ≥50% was found between both A. sulcata Kunitz-type protease inhibitors SA5 II, SA5 III and AsKC1 – AsKC15.

Kalicludine has 48% identity with the amyloid A4 homologue, which is implicated in Alzheimer's disease.^[5]

The kalicludine isotoxins have similar molecular size and a similar biological function.^[6] They contain three amino acid residues that are important for trypsin binding: Lys-15, Ala-16, and Ile-19 in BPTI. AsKCs have a replacement at position 19 (Ile → Pro), which results in less inhibitory action than BPTI.^[7]