7ezc | pdb_00007ezc

Adenosine A2a receptor mutant-I92N

spinqualitylabelsall models 7ezc, resolution 3.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7ezc is a 2 chain structure with sequence from Escherichia coli and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.8Å Ligands: UKA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function AA2AR_HUMAN Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.C562_ECOLX Electron-transport protein of unknown function. Publication Abstract from PubMed The adenosine A2A receptor (A2AAR) is a prototypical member of the class A subfamily of G-protein-coupled receptors (GPCRs) that is widely distributed in various tissues and organs of the human body, and participates in many important signal-regulation processes. We have previously summarized a common activation pathway of class A GPCRs in which a series of conserved residues/motifs undergo conformational change during extracellular agonist binding and finally induce the coupling of intracellular G protein. Through this mechanism we have successfully predicted several novel constitutive active or inactive mutations for A2AAR. To reveal the molecular mechanism of mutation-induced constitutive activity, we determined the structure of a typical mutant I92N complexed with the agonist UK-432097. The mutated I92N forms a hydrophilic interaction network with nearby residues including Trp(6.48) of the CWxP motif, which is absent in wild-type A2AAR. Although the mutant structure is similar overall to the previously determined intermediate-state A2AAR structure (PDB ID 3qak) [Xu, Wu, Katritch, Han, Jacobson, Gao, Cherezov & Stevens (2011). Science, 332, 322-327 black triangle right], molecular dynamics simulations suggest that the I92N mutant stabilizes the metastable intermediate state through the hydrophilic interaction network and favors the conformational transition of the receptor towards the active state. This research provides a structural template towards the special pharmacological outcome triggered by conformational mutation and sheds light on future structural or pharmaco-logical studies among class A GPCRs. Crystal structure of a constitutive active mutant of adenosine A2A receptor.,Cui M, Zhou Q, Xu Y, Weng Y, Yao D, Zhao S, Song G IUCrJ. 2022 Mar 17;9(Pt 3):333-341. doi: 10.1107/S2052252522001907. eCollection, 2022 May 1. PMID:35546802 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Adenosine A2A receptor 3D structures

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