6WQR
NMR solution structure of leech peptide HSTX-I
Summary for 6WQR
| Entry DOI | 10.2210/pdb6wqr/pdb |
| NMR Information | BMRB: 30750 |
| Descriptor | HSTX-I (1 entity in total) |
| Functional Keywords | disulfide-rich, antiparallel beta-sheet, hydrophobic, toxin |
| Biological source | Haemadipsa sylvestris (Indian leech) |
| Total number of polymer chains | 1 |
| Total formula weight | 2625.18 |
| Authors | Schroeder, C.I.,McMahon, K.L. (deposition date: 2020-04-29, release date: 2020-06-24, Last modification date: 2024-11-06) |
| Primary citation | McMahon, K.L.,Tay, B.,Deuis, J.R.,Tanaka, B.S.,Peigneur, S.,Jin, A.H.,Tytgat, J.,Waxman, S.G.,Dib-Hajj, S.D.,Vetter, I.,Schroeder, C.I. Pharmacological activity and NMR solution structure of the leech peptide HSTX-I. Biochem Pharmacol, 181:114082-114082, 2020 Cited by PubMed Abstract: The role of voltage-gated sodium (Na) channels in pain perception is indisputable. Of particular interest as targets for the development of pain therapeutics are the tetrodotoxin-resistant isoforms Na1.8 and Na1.9, based on animal as well as human genetic studies linking these ion channel subtypes to the pathogenesis of pain. However, only a limited number of inhibitors selectively targeting these channels have been reported. HSTX-I is a peptide toxin identified from saliva of the leech Haemadipsa sylvestris. The native 23-residue peptide, stabilised by two disulfide bonds, has been reported to inhibit rat Na1.8 and mouse Na1.9 with low micromolar activity, and may therefore represent a scaffold for development of novel modulators with activity at human tetrodotoxin-resistant Na isoforms. We synthetically produced this hydrophobic peptide in high yield using a one-pot oxidation and single step purification and determined the three-dimensional solution structure of HSTX-I using NMR solution spectroscopy. However, in our hands, the synthetic HSTX-I displayed only very modest activity at human Na1.8 and Na1.9, and lacked analgesic efficacy in a murine model of inflammatory pain. PubMed: 32524995DOI: 10.1016/j.bcp.2020.114082 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
Download full validation report
