1C49

STRUCTURAL AND FUNCTIONAL DIFFERENCES OF TWO TOXINS FROM THE SCORPION PANDINUS IMPERATOR

Summary for 1C49

• Entry DOI: 10.2210/pdb1c49/pdb
• NMR Information: BMRB: 4760
• Descriptor: TOXIN K-BETA (1 entity in total)
• Functional Keywords: scorpion toxin, potassium channels blockers, alpha-k toxin family, neurotoxin, nmr solution structure, toxin
• Biological source: Pandinus imperator (emperor scorpion)
• Cellular location: Secreted: P55928
• Total number of polymer chains: 1
• Total formula weight: 4080.82

Authors

Klenk, K.C.,Tenenholz, T.C.,Matteson, D.R.,Rogowski, R.S.,Blaustein, M.P.,Weber, D.J. (deposition date: 1999-08-17, release date: 2000-03-22, Last modification date: 2024-10-30)

Primary citation

Klenk, K.C.,Tenenholz, T.C.,Matteson, D.R.,Rogowski, R.S.,Blaustein, M.P.,Weber, D.J.
Structural and functional differences of two toxins from the scorpion Pandinus imperator.
Proteins, 38:441-449, 2000

PubMed Abstract: The Pandinotoxins, PiTX-K alpha and PiTX-K beta, are members of the Charybdotoxin family of scorpion toxins that can be used to characterize K+ channels. PiTX-K alpha differs from PiTX-K beta, another peptide from Pandinus imperator, by one residue (P10E). When the two toxins are compared in a physiological assay, the affinity of PiTX-K beta for voltage-gated, rapidly inactivating K+ channels in dorsal root ganglia (DRG) neurons is 800-fold lower than that of PiTX-K alpha (K alpha-IC50 = 8.0 nM versus K beta-IC50 = 6,500 nM). To understand this difference, the three-dimensional structure of PiTX-K beta was determined by nuclear magnetic resonance (NMR) spectroscopy and compared to that of PiTX-K alpha. This comparison shows that structural differences between the two toxins occur at a residue that is critical for blocking K+ channels (K27) as well as at the site of the natural mutation (P10E). In PiTX-K beta, the negatively charged carboxylate oxygen of E10 can approach the positive charge of K27 and presumably reduces the net positive charge in this region of the toxin. This is likely the reason why PiTX-K beta binds K+ channels from DRG neurons with a much lower affinity than does PiTX-K alpha.

PubMed: 10707030
DOI: 10.1002/(SICI)1097-0134(20000301)38:4<441::AID-PROT9>3.3.CO;2-C

Experimental method

SOLUTION NMR