PDBsum entry 1c49

Toxin

PDB id: 1c49

Contents

Protein chain

35 a.a.

PDB id:

1c49

Name:

Toxin

Title:

Structural and functional differences of two toxins from the scorpion pandinus imperator

Structure:

Toxin k-beta. Chain: a. Fragment: complete peptide. Synonym: pitx-kb, alpha-ktx5.2. Engineered: yes

Source:

Pandinus imperator. Emperor scorpion. Organism_taxid: 55084. Tissue: venom. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

NMR struc:

18 models

Authors:

K.C.Klenk,T.C.Tenenholz,D.R.Matteson,R.S.Rogowski,M.P.Blaustein, D.J.Weber

Key ref:

K.C.Klenk et al. (2000). Structural and functional differences of two toxins from the scorpion Pandinus imperator. Proteins, 38, 441-449. PubMed id: 10707030 DOI: 10.1002/(SICI)1097-0134(20000301)38:4<441::AID-PROT9>3.3.CO;2-C

Date:

17-Aug-99 Release date: 22-Mar-00

Protein chain

P55928  (KAX72_PANIM) -  Potassium channel toxin alpha-KTx 7.2 from Pandinus imperator

Seq: 35 a.a.

Struc: 35 a.a.

DOI no: 10.1002/(SICI)1097-0134(20000301)38:4<441::AID-PROT9>3.3.CO;2-C

Proteins 38:441-449 (2000)

PubMed id: 10707030

Structural and functional differences of two toxins from the scorpion Pandinus imperator.

K.C.Klenk, T.C.Tenenholz, D.R.Matteson, R.S.Rogowski, M.P.Blaustein, D.J.Weber.

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.

Selected figure(s)

Figure 1.
Figure 1. Chemical shift differences between PiTX-K and PiTX-K . The difference of the chemical shifts for all detected amide (gray bars) and alpha (black bars) is shown as the absolute value of PiTX-K minus PiTX-K . For side-chain protons, the absolute value of the largest difference in the side chain is shown (striped bars), and labeled appropriately.

Figure 5.
Figure 5. pH dependence of the chemical shifts of the protons of E10 ( , ), the protons of K27 ( ), and the protons of K27 ( ) of PiTX-K . These data are all consistent with a pK[a] of <3.5 for protonation of E10 in PiTX-K .

The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2000, 38, 441-449) copyright 2000.

Figures were selected by the author.