2PTA

PANDINUS TOXIN K-A (PITX-KA) FROM PANDINUS IMPERATOR, NMR, 20 STRUCTURES


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 500 
  • Conformers Submitted: 20 
  • Selection Criteria: NO DISTANCE VIOLATIONS GREATER THAN 0.30 ANGSTROMS, NO ANGULAR VIOLATIONS > 5 DEG, TOTAL ENERGY < 120 KCAL/MOL 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Solution structure for Pandinus toxin K-alpha (PiTX-K alpha), a selective blocker of A-type potassium channels.

Tenenholz, T.C.Rogowski, R.S.Collins, J.H.Blaustein, M.P.Weber, D.J.

(1997) Biochemistry 36: 2763-2771

  • DOI: https://doi.org/10.1021/bi9628432
  • Primary Citation of Related Structures:  
    2PTA

  • PubMed Abstract: 

    PiTX-K alpha, a 35-residue peptide recently isolated from the venom of Pandinus imperator, blocks the rapidly inactivating (A-type) K+ channel(s) in rat brain synaptosomes and the cloned Kv 1.2 potassium channel at very low toxin concentrations (6 nM and 32 pM, respectively) [Rogowski, R. S., Collins, J. H., O'Neil, T. J., Gustafson, T. A., Werkman, T. A., Rogawski, M. A., Tenenholz, T. C., Weber, D. J., & Blaustein, M. P. (1996) Mol. Pharmacol. 50, 1167-1177]. The three-dimensional structure of PiTX-K alpha was determined using NMR spectroscopy in order to understand its selectivity and affinity toward K+ channels. PiTX-K alpha was found to have an alpha-helix from residues 10 to 21 and two beta-strands (betaI, 26-28; betaII, 33-35) connected by a type II beta-turn to form a small antiparallel beta-sheet. Three disulfide bonds, which are conserved in all members of the charybdotoxin family (alpha-K toxins), anchor one face of the alpha-helix to the beta-sheet. The N-terminal portion of PiTX-K alpha has three fewer residues than other alpha-K toxins such as charybdotoxin. Rather than forming a third beta-strand as found for other alpha-K toxins, the N-terminal region of PiTX-K alpha adopts an extended conformation. This structural difference in PiTX-K alpha together with differences in sequence at Pro-10, Tyr-14, and Asn-25 (versus Ser-10, Trp-14, and Arg-25 in CTX) may explain why PiTX-K alpha does not block maxi-K+ channels. Differences in three-dimensional structure between PiTX-K alpha and charybdotoxin are also observed in both the tight turn and the loop that connects the first beta-strand to the alpha-helix. As a result, side chains of two residues (Tyr-23 and Arg-31) are in regions of PiTX-K alpha that probably interact with rapidly inactivating A-type K+ channels. The analogous residues in charybdotoxin are positioned differently on the toxin surface. Thus, the locations of Tyr-23 and Arg-31 side chains in PiTX-K alpha could explain why this toxin blocks A-type channels at much lower concentrations than does charybdotoxin.


  • Organizational Affiliation

    Department of Biochemistry, University of Maryland School of Medicine, Baltimore 21201, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PANDINUS TOXIN K-ALPHA35Pandinus imperatorMutation(s): 0 
UniProt
Find proteins for P55927 (Pandinus imperator)
Explore P55927 
Go to UniProtKB:  P55927
Entity Groups  
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UniProt GroupP55927
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 500 
  • Conformers Submitted: 20 
  • Selection Criteria: NO DISTANCE VIOLATIONS GREATER THAN 0.30 ANGSTROMS, NO ANGULAR VIOLATIONS > 5 DEG, TOTAL ENERGY < 120 KCAL/MOL 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1997-12-10
    Type: Initial release
  • Version 1.1: 2008-03-25
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-11-29
    Changes: Derived calculations, Other