6lry
From Proteopedia
Crystal structure of human endothelin ETB receptor in complex with sarafotoxin S6b
Structural highlights
Disease[EDNRB_HUMAN] Hirschsprung disease;Waardenburg-Shah syndrome. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Defects in EDNRB are associated with Waardenburg syndrome 2, with ocular albinism, autosomal recessive: A disorder characterized by the association of features typical of Waardenburg syndrome type 2 with ocular albinism. Patients manifest reduced visual acuity, albinotic fundus, deafness, hypomelanosis.[1] Function[EDNRB_HUMAN] Non-specific receptor for endothelin 1, 2, and 3. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.[2] [SRTX_ATREN] Vasoconstrictor activity. These toxins cause cardiac arrest probably as a result of coronary vasospasm.[3] Sarafotoxin-B: vasoconstrictor activity. Causes cardiac arrest probably as a result of coronary vasospasm (By similarity). Displays high agonistic activities towards endothelin-2 receptor (EDNRB) (displays affinity in the picomolar range) and endothelin-1 receptor (EDNRA) (lower affinities) (PubMed:21889567).[4] Publication Abstract from PubMedSarafotoxins (SRTXs) are endothelin-like peptides extracted from snake venom. SRTXs stimulate the endothelin ETA and ETB receptors and enhance vasoconstriction, followed by left ventricular dysfunction and bronchoconstriction. SRTXs include four major isopeptides, S6a-d, with different subtype selectivities. Here, we report the crystal structure of the human ETB receptor in complex with the non-selective sarafotoxin S6b at 3.0 A resolution. This structure reveals the similarities and differences between the binding modes of the endothelins and S6b. Moreover, molecular dynamics simulations based on the S6b-bound receptor provides structural insight into the subtype selectivity of the sarafotoxins. Our study clarifies the recognition mechanism of the endothelin-like peptide families. Crystal structure of human endothelin ETB receptor in complex with sarafotoxin S6b.,Izume T, Miyauchi H, Shihoya W, Nureki O Biochem Biophys Res Commun. 2020 Jan 28. pii: S0006-291X(20)30021-8. doi:, 10.1016/j.bbrc.2019.12.091. PMID:32001000[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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