2Z3S
NMR structure of AgTx2-MTX
Summary for 2Z3S
| Entry DOI | 10.2210/pdb2z3s/pdb |
| NMR Information | BMRB: 15299 |
| Descriptor | AgTx2-MTX (1 entity in total) |
| Functional Keywords | toxin, inhibitory cystine knot, chimera, maurotoxin, agitoxin |
| Total number of polymer chains | 1 |
| Total formula weight | 4107.85 |
| Authors | Pimentel, C.,M'Barrek, S.,Visan, V.,Grissmer, S.,Sabatier, J.M.,Darbon, H.,Fajloun, Z. (deposition date: 2007-06-06, release date: 2008-04-22, Last modification date: 2024-10-30) |
| Primary citation | Pimentel, C.,M'Barek, S.,Visan, V.,Grissmer, S.,Sampieri, F.,Sabatier, J.M.,Darbon, H.,Fajloun, Z. Chemical synthesis and 1H-NMR 3D structure determination of AgTx2-MTX chimera, a new potential blocker for Kv1.2 channel, derived from MTX and AgTx2 scorpion toxins. Protein Sci., 17:107-118, 2008 Cited by PubMed Abstract: Agitoxin 2 (AgTx2) is a 38-residue scorpion toxin, cross-linked by three disulfide bridges, which acts on voltage-gated K(+) (Kv) channels. Maurotoxin (MTX) is a 34-residue scorpion toxin with an uncommon four-disulfide bridge reticulation, acting on both Ca(2+)-activated and Kv channels. A 39-mer chimeric peptide, named AgTx2-MTX, was designed from the sequence of the two toxins and chemically synthesized. It encompasses residues 1-5 of AgTx2, followed by the complete sequence of MTX. As established by enzyme cleavage, the new AgTx2-MTX molecule displays half-cystine pairings of the type C1-C5, C2-C6, C3-C7, and C4-C8, which is different from that of MTX. The 3D structure of AgTx2-MTX solved by (1)H-NMR, revealed both alpha-helical and beta-sheet structures, consistent with a common alpha/beta scaffold of scorpion toxins. Pharmacological assays of AgTx2-MTX revealed that this new molecule is more potent than both original toxins in blocking rat Kv1.2 channel. Docking simulations, performed with the 3D structure of AgTx2-MTX, confirmed this result and demonstrated the participation of the N-terminal domain of AgTx2 in its increased affinity for Kv1.2 through additional molecular contacts. Altogether, the data indicated that replacement of the N-terminal domain of MTX by the one of AgTx2 in the AgTx2-MTX chimera results in a reorganization of the disulfide bridge arrangement and an increase of affinity to the Kv1.2 channel. PubMed: 18042681DOI: 10.1110/ps.073122908 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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