8gwe

SARS-CoV-2 E-RTC complex with RNA-nsp9 and GMPPNP

spinqualitylabelsall models 8gwe, resolution 2.66Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8gwe is a 10 chain structure with sequence from Severe acute respiratory syndrome coronavirus 2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.66Å Ligands: GNP, MG, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Decoration of cap on viral RNA plays essential roles in SARS-CoV-2 proliferation. Here, we report a mechanism for SARS-CoV-2 RNA capping and document structural details at atomic resolution. The NiRAN domain in polymerase catalyzes the covalent link of RNA 5' end to the first residue of nsp9 (termed as RNAylation), thus being an intermediate to form cap core (GpppA) with GTP catalyzed again by NiRAN. We also reveal that triphosphorylated nucleotide analog inhibitors can be bonded to nsp9 and fit into a previously unknown "Nuc-pocket" in NiRAN, thus inhibiting nsp9 RNAylation and formation of GpppA. S-loop (residues 50-KTN-52) in NiRAN presents a remarkable conformational shift observed in RTC bound with sofosbuvir monophosphate, reasoning an "induce-and-lock" mechanism to design inhibitors. These findings not only improve the understanding of SARS-CoV-2 RNA capping and the mode of action of NAIs but also provide a strategy to design antiviral drugs. A mechanism for SARS-CoV-2 RNA capping and its inhibition by nucleotide analog inhibitors.,Yan L, Huang Y, Ge J, Liu Z, Lu P, Huang B, Gao S, Wang J, Tan L, Ye S, Yu F, Lan W, Xu S, Zhou F, Shi L, Guddat LW, Gao Y, Rao Z, Lou Z Cell. 2022 Nov 10;185(23):4347-4360.e17. doi: 10.1016/j.cell.2022.09.037. Epub , 2022 Oct 4. PMID:36335936 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also RNA polymerase 3D structures

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