1ktx | pdb_00001ktx
KALIOTOXIN (1-37) SHOWS STRUCTURAL DIFFERENCES WITH RELATED POTASSIUM CHANNEL BLOCKERS
Structural highlights
Function[KAX31_ANDMA] Potent inhibitor of large conductance calcium-activated potassium channels (BK-Ca). Also binds to the dendrotoxin sensitive voltage-dependent potassium channel. It appears to block channel activity by a simple bimolecular inhibition process. Induces a transient period of fast flickering in the channel openings, followed by an almost complete blockade of the channel. Its binding affinity to rat brain synaptosomes is 5-fold higher than this of KTX-3. Binding of the toxin to the channel is associated with significant structural rearrangements in both molecules. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe three-dimensional structure of kaliotoxin (1-37), KTX(1-37), a toxin from the scorpion Androctonus mauretanicus mauretanicus that blocks calcium-dependent potassium channels, has been determined by NMR. This toxin is homologous with other scorpion toxins such as charybdotoxin (ChTX) or iberiotoxin (IbTX) for which the structures are already known, but the presence of prolines in the expected alpha-helical region suggested that there may be some major difference in the structure of KTX that could be related to its different selectivity. Proline residues are also found in the homologous region of other scorpion toxins such as noxiustoxin or margatoxin. Our results indicate that KTX(1-37) contains the same sequence of secondary structure elements as ChTX but that the helical region is shorter and distorted due to the presence of two prolines. The distortion consists of a bending in the alpha-helix and in the presence of a 3(10) helix turn in the last three residues. Furthermore, the increased length of the extended structure preceding the helix favors a different packing of this part of the molecule with respect to the secondary structure elements. This change in folding modifies the accessibility of the conserved 27Lys which is known, from mutation studies, to be involved in channel blocking by ChTX. Kaliotoxin (1-37) shows structural differences with related potassium channel blockers.,Fernandez I, Romi R, Szendeffy S, Martin-Eauclaire MF, Rochat H, Van Rietschoten J, Pons M, Giralt E Biochemistry. 1994 Nov 29;33(47):14256-63. PMID:7524673[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences | ||||||||||||||||||
