2CA7

Conkunitzin-S1 Is The First Member Of A New Kunitz-Type Neurotoxin Family- Structural and Functional Characterization

Replaces:  1YL2

Summary for 2CA7

• Entry DOI: 10.2210/pdb2ca7/pdb
• NMR Information: BMRB: 6506
• Descriptor: CONKUNITZIN-S1 (1 entity in total)
• Functional Keywords: conkunitzin, neurotoxin, toxin, kunitz-type fold, potassium channel inhibitor, kunitz-domain
• Biological source: CONUS STRIATUS
• Total number of polymer chains: 1
• Total formula weight: 6944.69

Authors

Bayrhuber, M.,Vijayan, V.,Ferber, M.,Graf, R.,Korukottu, J.,Imperial, J.,Garrett, J.E.,Olivera, B.M.,Terlau, H.,Zweckstetter, M.,Becker, S. (deposition date: 2005-12-19, release date: 2006-01-05, Last modification date: 2024-11-13)

Primary citation

Bayrhuber, M.,Vijayan, V.,Ferber, M.,Graf, R.,Korukottu, J.,Imperial, J.,Garrett, J.E.,Olivera, B.M.,Terlau, H.,Zweckstetter, M.,Becker, S.
Conkunitzin-S1 is the first member of a new Kunitz-type neurotoxin family. Structural and functional characterization.
J. Biol. Chem., 280:23766-23770, 2005

PubMed Abstract: Conkunitzin-S1 (Conk-S1) is a 60-residue neurotoxin from the venom of the cone snail Conus striatus that interacts with voltage-gated potassium channels. Conk-S1 shares sequence homology with Kunitz-type proteins but contains only two out of the three highly conserved cysteine bridges, which are typically found in these small, basic protein modules. In this study the three-dimensional structure of Conk-S1 has been solved by multidimensional NMR spectroscopy. The solution structure of recombinant Conk-S1 shows that a Kunitz fold is present, even though one of the highly conserved disulfide cross-links is missing. Introduction of a third, homologous disulfide bond into Conk-S1 results in a functional toxin with similar affinity for Shaker potassium channels. The affinity of Conk-S1 can be enhanced by a pore mutation within the Shaker channel pore indicating an interaction of Conk-S1 with the vestibule of potassium channels.

PubMed: 15833744
DOI: 10.1074/jbc.C500064200

Experimental method

SOLUTION NMR