Solution structure of TsKapa, a charybdotoxin-like scorpion toxin from Tityus serrulatus with high affinity for apamin-sensitive Ca(2+)-activated K+ channels

Autor: Blanc, E., Hassani, O., Meunier, S., Mansuelle, P., Sampieri, F., Rochat, H., Darbon, H., Lecomte, C., Rietschoten, J. V., Sabatier, J. M.
Přispěvatelé: Architecture et fonction des macromolécules biologiques (AFMB), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Blanc, Eric, Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)
Jazyk: angličtina
Rok vydání: 1997
Předmět:
MESH: Molecular Sequence Data
MESH: Magnetic Resonance Spectroscopy
MESH: Sequence Homology
Amino Acid
MESH: Protein Folding
MESH: Protein Structure
Secondary
MESH: Potassium Channels
MESH: Amino Acid Sequence
MESH: Solutions
MESH: Scorpions
MESH: Small-Conductance Calcium-Activated Potassium Channels
[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Biomolecules [q-bio.BM]
MESH: Protein Conformation
MESH: Scorpion Venoms
MESH: Structure-Activity Relationship
MESH: Potassium Channels
Calcium-Activated
MESH: Calcium
MESH: Nuclear Magnetic Resonance
Biomolecular
MESH: Animals
MESH: Hydrogen Bonding
MESH: Protons
[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Biochemistry [q-bio.BM]
MESH: Charybdotoxin
[SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry
Molecular Biology/Biochemistry [q-bio.BM]
MESH: Apamin
Zdroj: Proteins-Structure, Function and Bioinformatics
Proteins-Structure, Function and Bioinformatics, Wiley, 1997, 29 (3), pp.359-69
Proteins-Structure, Function and Bioinformatics, 1997, 29 (3), pp.359-69
ISSN: 0887-3585
1097-0134
Popis: International audience; TsKapa (TsK), purified from the Buthidae Tityus serrulatus is a very high potent ligand for small-conductance apamin-sensitive calcium-activated potassium channels (SK). It is able to efficiently compete with apamin for binding on this channel (K0.5 = 0.3 nM) [Legros, C. et al., FEBS Lett. 390:81-84, 1996]. The solution structure of TsK has been determined by 2D-NMR techniques, which led to the full description of its 3D conformation: a short alpha helix from residues 14 to 20 and a three-stranded antiparallel beta sheet (residues 2-3, 27-29, and 32-34). The interaction of TsK with the SK potassium channel has been modeled according to the charge anisotropy of the ligand. The resulting dipole moment orientates TsK so that it presents toward the receptor, a surface, mainly basic, encompassing residues K18 and K19 on one side and R9 and Y8 on the other. Despite its three-dimensional structure that is related with scorpion toxins active on voltage-gated potassium channels such as charybdotoxin, the pharmacological activity and specificity of TsK is related with shorter scorpion toxins (i.e., possessing an only two-stranded beta sheet) such as scyllatoxin (also named leiurotoxin I) or P05.
Databáze: OpenAIRE
Externí odkaz: