5O0U
Crystal structure of tarantula venom peptide Protoxin-II
Summary for 5O0U
| Entry DOI | 10.2210/pdb5o0u/pdb |
| Descriptor | Beta/omega-theraphotoxin-Tp2a, CHLORIDE ION, 1,2-ETHANEDIOL, ... (4 entities in total) |
| Functional Keywords | inhibitor cystine knot, ion channel inhibitors, venom, toxin |
| Biological source | Thrixopelma pruriens (green velvet) |
| Total number of polymer chains | 1 |
| Total formula weight | 4034.73 |
| Authors | Tabor, A.,McCarthy, S.,Reyes, F.E. (deposition date: 2017-05-17, release date: 2017-09-13, Last modification date: 2024-10-16) |
| Primary citation | Wright, Z.V.F.,McCarthy, S.,Dickman, R.,Reyes, F.E.,Sanchez-Martinez, S.,Cryar, A.,Kilford, I.,Hall, A.,Takle, A.K.,Topf, M.,Gonen, T.,Thalassinos, K.,Tabor, A.B. The Role of Disulfide Bond Replacements in Analogues of the Tarantula Toxin ProTx-II and Their Effects on Inhibition of the Voltage-Gated Sodium Ion Channel Nav1.7. J.Am.Chem.Soc., 139:13063-13075, 2017 Cited by PubMed Abstract: Spider venom toxins, such as Protoxin-II (ProTx-II), have recently received much attention as selective Na1.7 channel blockers, with potential to be developed as leads for the treatment of chronic nocioceptive pain. ProTx-II is a 30-amino acid peptide with three disulfide bonds that has been reported to adopt a well-defined inhibitory cystine knot (ICK) scaffold structure. Potential drawbacks with such peptides include poor pharmacodynamics and potential scrambling of the disulfide bonds in vivo. In order to address these issues, in the present study we report the solid-phase synthesis of lanthionine-bridged analogues of ProTx-II, in which one of the three disulfide bridges is replaced with a thioether linkage, and evaluate the biological properties of these analogues. We have also investigated the folding and disulfide bridging patterns arising from different methods of oxidation of the linear peptide precursor. Finally, we report the X-ray crystal structure of ProTx-II to atomic resolution; to our knowledge this is the first crystal structure of an ICK spider venom peptide not bound to a substrate. PubMed: 28880078DOI: 10.1021/jacs.7b06506 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (0.99 Å) |
Structure validation
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