Maurotoxin: Difference between revisions

Maurotoxin is a peptide of 34 [[amino acid]]s (sequence VSCTGSKDCYAPCRKQTGCPNAKCINKSCKCYGC) cross-linked by four [[disulfide bridge]]s (Cys3-Cys24, Cys9-Cys29, Cys13-Cys19, Cys31-Cys34), with an atypical pattern of organization compared with other scorpion toxins; this unusual pairing of [[cysteine]] residues may be mediated by the presence of adjacent [[proline]]s. The peptide contains an [[alpha helix]] linked by two disulfide bridges to a two-stranded antiparallel [[beta sheet]].

* [[Apamin]]-sensitive small conductance [[calcium|Ca²⁺]] - activated [[potassium|K⁺]] channels (SK)

* Several types of [[voltage-gated Kvpotassium channelschannel]]s (Kv1.1, Kv1.2, Kv1.3 and shaker B)

The intermediate conductance Ca²⁺-activated K⁺ (IK) channel is present in peripheral tissues, including secretory [[epithelia]] and [[blood cellscell]]s. An important physiological role of the IK channel is to help maintain large electrical gradients for the sustained transport of ions such as Ca²⁺ that controls [[T lymphocyte]] (T cell) proliferation. HerebyThus IK blockers could be potential immunosuppressants[[immunosuppressant]]s for the treatment of autoimmune disorders (such as rheumatoid arthritis, inflammatory bowel disease and multiple sclerosis).

MTX occludes the pore region of various potassium channels (Kv1.2, IKCa1, Kv1.3) by establishing strong interactions between its Lys23[[lysine]]-23 residue and the [[glycine]]-[[tyrosine]]-[[glycine]]-[[aspartate]] (GYGD) motif of the channel. MTX thus blocks the channels by binding in the external vestibule of the pore to block the ion conduction pathway. Although Kv1.1, Kv1.2, and Kv1.3 have a very similar pore structure, they display different pharmacological sensitivity to MTX.

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# Visan, V., ''et al.'', Mapping of maurotoxin binding sites on hKv1.2, hKv1.3, and hIKCa1 channels. Mol Pharmacol, 2004. 66(5): p. 1103-121103–12.