Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structural basis of antagonist selectivity in endothelin receptors.
Journal, issue, pages	Cell Discov, Vol. 10, Issue 1, Page 79, Year 2024
Publish date	Jul 30, 2024
Authors	Junyi Hou / Shenhui Liu / Xiaodan Zhang / Guowei Tu / Lijie Wu / Yijie Zhang / Hao Yang / Xiangcheng Li / Junlin Liu / Longquan Jiang / Qiwen Tan / Fang Bai / Zhijie Liu / Changhong Miao / Tian Hua / Zhe Luo /
PubMed Abstract	Endothelins and their receptors, ET and ET, play vital roles in maintaining vascular homeostasis. Therapeutically targeting endothelin receptors, particularly through ET antagonists, has shown ...Endothelins and their receptors, ET and ET, play vital roles in maintaining vascular homeostasis. Therapeutically targeting endothelin receptors, particularly through ET antagonists, has shown efficacy in treating pulmonary arterial hypertension (PAH) and other cardiovascular- and renal-related diseases. Here we present cryo-electron microscopy structures of ET in complex with two PAH drugs, macitentan and ambrisentan, along with zibotentan, a selective ET antagonist, respectively. Notably, a specialized anti-ET antibody facilitated the structural elucidation. These structures, together with the active-state structures of ET-1-bound ET and ET, and the agonist BQ3020-bound ET, in complex with G, unveil the molecular basis of agonist/antagonist binding modes in endothelin receptors. Key residues that confer antagonist selectivity to endothelin receptors were identified along with the activation mechanism of ET. Furthermore, our results suggest that ECL2 in ET can serve as an epitope for antibody-mediated receptor antagonism. Collectively, these insights establish a robust theoretical framework for the rational design of small-molecule drugs and antibodies with selective activity against endothelin receptors.
External links	Cell Discov / PubMed:39075075 / PubMed Central
Methods	EM (single particle)
Resolution	3.0 - 3.32 Å
Structure data	38702 8xve EMDB-38702, PDB-8xve: Cryo-EM structure of ETBR bound with BQ3020 Method: EM (single particle) / Resolution: 3.0 Å 38704 8xvh EMDB-38704, PDB-8xvh: Cryo-EM structure of ETBR bound with Endothelin1 Method: EM (single particle) / Resolution: 3.26 Å 38705 8xvi EMDB-38705, PDB-8xvi: Cryo-EM structure of ETAR bound with Endothelin1 Method: EM (single particle) / Resolution: 3.32 Å 38706 8xvj EMDB-38706, PDB-8xvj: Cryo-EM structure of ETAR bound with Macitentan Method: EM (single particle) / Resolution: 3.26 Å 38707 8xvk EMDB-38707, PDB-8xvk: Cryo-EM structure of ETAR bound with Ambrisentan Method: EM (single particle) / Resolution: 3.21 Å 38708 8xvl EMDB-38708, PDB-8xvl: Cryo-EM structure of ETAR bound with Zibotentan Method: EM (single particle) / Resolution: 3.22 Å
Chemicals	PDB-1d5i: UNLIGANDED GERMLINE PRECURSOR OF AN OXY-COPE CATALYTIC ANTIBODY PDB-1d5j: CRYSTAL STRUCTURE OF MMP3 COMPLEXED WITH A THIAZEPINE BASED INHIBITOR. PDB-1d5l: CRYSTAL STRUCTURE OF CYANIDE-BOUND HUMAN MYELOPEROXIDASE ISOFORM C AT PH 5.5
Source	homo sapiens (human) lama glama (llama) synthetic construct (others) clostridium perfringens (bacteria) acetivibrio thermocellus atcc 27405 (bacteria) acetivibrio thermocellus (strain atcc 27405 / dsm 1237 / jcm 9322 / nbrc 103400 / ncimb 10682 / nrrl b-4536 / vpi 7372) (bacteria) escherichia coli (E. coli)
Keywords	SIGNALING PROTEIN / GPCR / COMPLEX / ETB / BQ3020 / ENDOTHELIN-1 / ETA / MACITENTAN / AMBRISENTAN / ZIBOTENTAN