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 insights into the agonist selectivity of the adenosine A receptor.
Journal, issue, pages	Nat Commun, Vol. 15, Issue 1, Page 9294, Year 2024
Publish date	Nov 7, 2024
Authors	Hidetaka S Oshima / Akiko Ogawa / Fumiya K Sano / Hiroaki Akasaka / Tomoyoshi Kawakami / Aika Iwama / Hiroyuki H Okamoto / Chisae Nagiri / Fan-Yan Wei / Wataru Shihoya / Osamu Nureki /
PubMed Abstract	Adenosine receptors play pivotal roles in physiological processes. Adenosine A receptor (AR), the most recently identified adenosine receptor, is expressed in various tissues, exhibiting important ...Adenosine receptors play pivotal roles in physiological processes. Adenosine A receptor (AR), the most recently identified adenosine receptor, is expressed in various tissues, exhibiting important roles in neuron, heart, and immune cells, and is often overexpressed in tumors, highlighting the therapeutic potential of AR-selective agents. Recently, we identified RNA-derived N-methyladenosine (mA) as an endogenous agonist for AR, suggesting the relationship between RNA-derived modified adenosine and AR. Despite extensive studies on the other adenosine receptors, the selectivity mechanism of AR, especially for AR-selective agonists such as mA and namodenoson, remained elusive. Here, we identify tRNA-derived N-isopentenyl adenosine (iA) as an AR-selective ligand via screening of modified nucleosides against the adenosine receptors. Like mA, iA is found in the human body and may be an endogenous AR ligand. Our cryo-EM analyses elucidate the AR-G complexes bound to adenosine, 5'-N-ethylcarboxamidoadenosine (NECA), mA, iA, and namodenoson at overall resolutions of 3.27 Å (adenosine), 2.86 Å (NECA), 3.19 Å (mA), 3.28 Å (iA), and 3.20 Å (namodenoson), suggesting the selectivity and activation mechanism of AR. We further conduct structure-guided engineering of mA-insensitive AR, which may aid future research targeting mA and AR, providing a molecular basis for future drug discovery.
External links	Nat Commun / PubMed:39511145 / PubMed Central
Methods	EM (single particle)
Resolution	2.75 - 3.66 Å
Structure data	39278 8yh0 EMDB-39278, PDB-8yh0: A3R-Gi complex bound to NECA Method: EM (single particle) / Resolution: 2.86 Å 39279 8yh2 EMDB-39279, PDB-8yh2: A3R-Gi complex bound to adenosine Method: EM (single particle) / Resolution: 3.27 Å 39280 8yh3 EMDB-39280, PDB-8yh3: A3R-Gi complex bound to m6A Method: EM (single particle) / Resolution: 3.4 Å 39281 8yh5 EMDB-39281, PDB-8yh5: A3R-Gi complex bound to i6A Method: EM (single particle) / Resolution: 3.66 Å 39282 8yh6 EMDB-39282, PDB-8yh6: A3R-Gi complex bound to namodenoson Method: EM (single particle) / Resolution: 3.62 Å EMDB-61664: A3R-Gi complex bound to NECA (G protein focused) Method: EM (single particle) / Resolution: 2.75 Å EMDB-61666: A3R-Gi complex bound to NECA (receptor focused) Method: EM (single particle) / Resolution: 3.04 Å EMDB-61668: A3R-Gi complex bound to adenosine (receptor focused) Method: EM (single particle) / Resolution: 3.41 Å EMDB-61670: A3R-Gi complex bound to adenosine (G protein focused) Method: EM (single particle) / Resolution: 3.19 Å EMDB-61673: A3R-Gi complex bound to m6a (receptor focused) Method: EM (single particle) / Resolution: 3.44 Å EMDB-61674: A3R-Gi complex bound to NECA (G protein focused) Method: EM (single particle) / Resolution: 3.08 Å EMDB-61675: A3R-Gi complex bound to i6a (receptor focused) Method: EM (single particle) / Resolution: 3.41 Å EMDB-61676: A3R-Gi complex bound to i6a (G protein focused) Method: EM (single particle) / Resolution: 3.14 Å EMDB-61677: A3R-Gi complex bound to namodenoson (receptor focused) Method: EM (single particle) / Resolution: 3.38 Å EMDB-61678: A3R-Gi complex bound to namodenoson (G protein focused) Method: EM (single particle) / Resolution: 3.02 Å
Chemicals	ChemComp-NEC: N-ETHYL-5'-CARBOXAMIDO ADENOSINE ChemComp-ADN: ADENOSINE ChemComp-6MD: N-methyladenosine ChemComp-ZIR: N-(3-methylbut-2-en-1-yl)adenosine ChemComp, No image ChemComp-XS0: Unknown entry
Source	ovis aries (sheep) homo sapiens (human) rattus rattus (black rat) mus musculus (house mouse) human orthopneumovirus human respiratory syncytial virus bos taurus (cattle) influenza a virus (a/victoria/3/1975(h3n2))
Keywords	SIGNALING PROTEIN / GPCR / complex / adenosine receptor / adenosine / g protein