title: Solution structure of BmKK2, a new potassium channel blocker from the venom of chinese scorpion Buthus martensi Karsch.
abstract: A natural K+ channel blocker, BmKK2 (a member of scorpion toxin subfamily alpha-KTx 14), which is composed of 31 amino acid residues and purified from the venom of the Chinese scorpion Buthus martensi Karsch, was characterized using whole-cell patch-clamp recording in rat hippocampal neurons. The three dimensional structure of BmKK2 was determined with two-dimensional NMR spectroscopy and molecular modelling techniques. In solution this toxin adopted a common alpha/beta-motif, but showed distinct local conformation in the loop between alpha-helix and beta-sheet in comparison with typical short-chain scorpion toxins (e.g., CTX and NTX). Also, the alpha helix is shorter and the beta-sheet element is smaller (each strand consisted only two residues). The unusual structural feature of BmKK2 was attributed to the shorter loop between the alpha-helix and beta-sheet and the presence of two consecutive Pro residues at position 21 and 22 in the loop. Moreover, two models of BmKK2/hKv1.3 channel and BmKK2/rSK2 channel complexes were simulated with docking calculations. The results demonstrated the existence of a alpha-mode binding between the toxin and the channels. The model of BmKK2/rSK2 channel complex exhibited favorable contacts both in electrostatic and hydrophobic, including a network of five hydrogen bonds and bigger interface containing seven pairs of inter-residue interactions. In contrast, the model of BmKK2/hKv1.3 channel complex, containing only three pairs of inter-residue interactions, exhibited poor contacts and smaller interface. The results well explained its lower activity towards Kv channel, and predicted that it may prefer a type of SK channel with a narrower entryway as its specific receptor.
authors.affiliation: State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, People's Republic of China.
authors.forename: Naixia
authors.initials: N
authors.lastname: Zhang
authors.forename: Minghua
authors.initials: M
authors.lastname: Li
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.forename: Yuefeng
authors.initials: Y
authors.lastname: Wang
authors.forename: Gong
authors.initials: G
authors.lastname: Wu
authors.forename: Guoyuan
authors.initials: G
authors.lastname: Hu
authors.forename: Houming
authors.initials: H
authors.lastname: Wu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004553:Electric Conductivity; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D019906:Nuclear Magnetic Resonance, Biomolecular; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated; D017433:Protein Structure, Secondary; D051381:Rats; D017207:Rats, Sprague-Dawley; D012604:Scorpion Venoms / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D016415:Sequence Alignment; D051640:Small-Conductance Calcium-Activated Potassium Channels; D013329:Structure-Activity Relationship
chemical_list: C445369:KK toxin, Buthus martensi; C496899:Kcnn2 protein, rat; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D012604:Scorpion Venoms; D051640:Small-Conductance Calcium-Activated Potassium Channels