| Structural highlights
Function
3SI1A_DENAN Orthosteric antagonist of the alpha-1A adrenergic receptor (ADRA1A) with an affinity of 0.35 nM (PubMed:20015090). Has also affinity for ADRA1B > ADRA2C > ADRA1D (PubMed:23935897). Acts as a relaxant of smooth muscle. Reduces prostatic muscle tone as efficiently as tamsulosin (an antagonist presently used), but with fewer cardiovascular side effects (PubMed:23005263).[1] [2] [3] [4]
Publication Abstract from PubMed
rho-Da1a toxin from eastern green mamba (Dendroaspis angusticeps) venom is a polypeptide of 65 amino acids with a strong affinity for the G-protein-coupled alpha(1A)-adrenoceptor. This neurotoxin has been crystallized from resolubilized lyophilized powder, but the best crystals grew spontaneously during lyophilization. The crystals belonged to the trigonal space group P3(1)21, with unit-cell parameters a = b = 37.37, c = 66.05 A, and diffracted to 1.95 A resolution. The structure solved by molecular replacement showed strong similarities to green mamba muscarinic toxins.
Crystallization of recombinant green mamba rho-Da1a toxin during a lyophilization procedure and its structure determination.,Maiga A, Vera L, Marchetti C, Lorphelin A, Bellanger L, Mourier G, Servent D, Gilles N, Stura EA Acta Crystallogr Sect F Struct Biol Cryst Commun. 2013 Jun;69(Pt 6):704-9. doi:, 10.1107/S1744309113011470. Epub 2013 May 29. PMID:23722859[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Quinton L, Girard E, Maiga A, Rekik M, Lluel P, Masuyer G, Larregola M, Marquer C, Ciolek J, Magnin T, Wagner R, Molgo J, Thai R, Fruchart-Gaillard C, Mourier G, Chamot-Rooke J, Menez A, Palea S, Servent D, Gilles N. Isolation and pharmacological characterization of AdTx1, a natural peptide displaying specific insurmountable antagonism of the alpha1A-adrenoceptor. Br J Pharmacol. 2010 Jan 1;159(2):316-25. doi: 10.1111/j.1476-5381.2009.00532.x. , Epub 2009 Dec 15. PMID:20015090 doi:https://dx.doi.org/10.1111/j.1476-5381.2009.00532.x
- ↑ Maiga A, Mourier G, Quinton L, Rouget C, Gales C, Denis C, Lluel P, Senard JM, Palea S, Servent D, Gilles N. G protein-coupled receptors, an unexploited animal toxin targets: Exploration of green mamba venom for novel drug candidates active against adrenoceptors. Toxicon. 2012 Mar 15;59(4):487-96. doi: 10.1016/j.toxicon.2011.03.009. Epub 2011 , Mar 22. PMID:21419153 doi:https://dx.doi.org/10.1016/j.toxicon.2011.03.009
- ↑ Palea S, Maiga A, Guilloteau V, Rekik M, Guerard M, Rouget C, Rischmann P, Botto H, Camparo P, Lluel P, Gilles N. Effects of rho-Da1a a peptidic alpha(1) (A) -adrenoceptor antagonist in human isolated prostatic adenoma and anaesthetized rats. Br J Pharmacol. 2013 Feb;168(3):618-31. doi: 10.1111/j.1476-5381.2012.02231.x. PMID:23005263 doi:https://dx.doi.org/10.1111/j.1476-5381.2012.02231.x
- ↑ Maiga A, Merlin J, Marcon E, Rouget C, Larregola M, Gilquin B, Fruchart-Gaillard C, Lajeunesse E, Marchetti C, Lorphelin A, Bellanger L, Summers RJ, Hutchinson DS, Evans BA, Servent D, Gilles N. Orthosteric binding of rho-Da1a, a natural peptide of snake venom interacting selectively with the alpha1A-adrenoceptor. PLoS One. 2013 Jul 25;8(7):e68841. doi: 10.1371/journal.pone.0068841. Print 2013. PMID:23935897 doi:https://dx.doi.org/10.1371/journal.pone.0068841
- ↑ Maiga A, Vera L, Marchetti C, Lorphelin A, Bellanger L, Mourier G, Servent D, Gilles N, Stura EA. Crystallization of recombinant green mamba rho-Da1a toxin during a lyophilization procedure and its structure determination. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2013 Jun;69(Pt 6):704-9. doi:, 10.1107/S1744309113011470. Epub 2013 May 29. PMID:23722859 doi:10.1107/S1744309113011470
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