Kim, Ye-Ji Jo, Yejin Lee, Seung Eun Kim, Jungeun Choi, Jae-Pil Lee, Nayoung Won, Hyokyoung Woo, Dong Ho Yum, Seungshic 2024-06-07T05:30:51Z 2024-06-07T05:30:51Z 2024-06-07 2024-05 https://pubs.kist.re.kr/handle/201004/150035 We identified a new human voltage-gated potassium channel blocker, NnK-1, in the jellyfish Nemopilema nomurai based on its genomic information. The gene sequence encoding NnK-1 contains 5408 base pairs, with five introns and six exons. The coding sequence of the NnK-1 precursor is 894 nucleotides long and encodes 297 amino acids containing five presumptive ShK-like peptides. An electrophysiological assay demonstrated that the fifth peptide, NnK-1, which was chemically synthesized, is an effective blocker of hKv1.3, hKv1.4, and hKv1.5. Multiple-sequence alignment with cnidarian Shk-like peptides, which have Kv1.3-blocking activity, revealed that three residues ((3)Asp, (25)Lys, and (34)Thr) of NnK-1, together with six cysteine residues, were conserved. Therefore, we hypothesized that these three residues are crucial for the binding of the toxin to voltage-gated potassium channels. This notion was confirmed by an electrophysiological assay with a synthetic peptide (NnK-1 mu) where these three peptides were substituted with (3)Glu, (25)Arg, and (34)Met. In conclusion, we successfully identified and characterized a new voltage-gated potassium channel blocker in jellyfish that interacts with three different voltage-gated potassium channels. A peptide that interacts with multiple voltage-gated potassium channels has many therapeutic applications in various physiological and pathophysiological contexts. English Multidisciplinary Digital Publishing Institute (MDPI) Synthetic ShK-like Peptide from the Jellyfish Nemopilema nomurai Has Human Voltage-Gated Potassium-Channel-Blocking Activity Article 10.3390/md22050217 1 Marine Drugs, v.22, no.5 Marine Drugs 22 5 Y scie scopus 001233500200001 2-s2.0-85194130690 Chemistry, Medicinal Pharmacology & Pharmacy Pharmacology & Pharmacy Article TOXIN KV1.3 INHIBITOR TARGET toxin venom jellyfish Cnidaria genomic information electrophysiology