5MG9
Putative Ancestral Mamba toxin 1 (AncTx1-W28R/I38S)
Summary for 5MG9
| Entry DOI | 10.2210/pdb5mg9/pdb |
| Descriptor | AncTx1-W28R/I38S, S-1,2-PROPANEDIOL, 1,2-ETHANEDIOL, ... (6 entities in total) |
| Functional Keywords | ancestral mamba snake toxin, three-finger fold, ancestral toxin resurrection and engineering, aminergic toxin, toxin |
| Biological source | Dendroaspis angusticeps (Eastern green mamba) |
| Total number of polymer chains | 1 |
| Total formula weight | 7877.88 |
| Authors | Stura, E.A.,Tepshi, L.,Blanchet, G.,Mourier, G.,Servent, D. (deposition date: 2016-11-21, release date: 2017-05-03, Last modification date: 2024-11-06) |
| Primary citation | Blanchet, G.,Alili, D.,Protte, A.,Upert, G.,Gilles, N.,Tepshi, L.,Stura, E.A.,Mourier, G.,Servent, D. Ancestral protein resurrection and engineering opportunities of the mamba aminergic toxins. Sci Rep, 7:2701-2701, 2017 Cited by PubMed Abstract: Mamba venoms contain a multiplicity of three-finger fold aminergic toxins known to interact with various α-adrenergic, muscarinic and dopaminergic receptors with different pharmacological profiles. In order to generate novel functions on this structural scaffold and to avoid the daunting task of producing and screening an overwhelming number of variants generated by a classical protein engineering strategy, we accepted the challenge of resurrecting ancestral proteins, likely to have possessed functional properties. This innovative approach that exploits molecular evolution models to efficiently guide protein engineering, has allowed us to generate a small library of six ancestral toxin (AncTx) variants and associate their pharmacological profiles to key functional substitutions. Among these variants, we identified AncTx1 as the most α-adrenoceptor selective peptide known to date and AncTx5 as the most potent inhibitor of the three α2 adrenoceptor subtypes. Three positions in the ρ-Da1a evolutionary pathway, positions 28, 38 and 43 have been identified as key modulators of the affinities for the α and α adrenoceptor subtypes. Here, we present a first attempt at rational engineering of the aminergic toxins, revealing an epistasis phenomenon. PubMed: 28578406DOI: 10.1038/s41598-017-02953-0 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.801 Å) |
Structure validation
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