8RZD
SARS-CoV-2 nsp16-nsp10 in complex with SAM derivative inhibitor 9
This is a non-PDB format compatible entry.
Summary for 8RZD
| Entry DOI | 10.2210/pdb8rzd/pdb |
| Descriptor | 2'-O-methyltransferase nsp16, Non-structural protein 10, 3-[[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methylsulfanylmethyl]-5-(3-hydroxyphenyl)benzoic acid, ... (6 entities in total) |
| Functional Keywords | nsp16, nsp10, 2'-o-methyltransferase, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 More |
| Total number of polymer chains | 2 |
| Total formula weight | 49615.49 |
| Authors | Kalnins, G. (deposition date: 2024-02-12, release date: 2024-02-21, Last modification date: 2024-10-02) |
| Primary citation | Kalnins, G.,Rudusa, L.,Bula, A.,Zelencova-Gopejenko, D.,Bobileva, O.,Sisovs, M.,Tars, K.,Jirgensons, A.,Jaudzems, K.,Bobrovs, R. Structural basis for inhibition of the SARS-CoV-2 nsp16 by substrate-based dual site inhibitors. Chemmedchem, :e202400618-e202400618, 2024 Cited by PubMed Abstract: Coronaviruses, including SARS-CoV-2, possess an mRNA 5' capping apparatus capable of mimicking the natural eukaryotic capping signature. Two SAM-dependent methylating enzymes play important roles in this process: nsp14 methylates the N7 of the guanosine cap, and nsp16-nsp10 methylates the 2'-O- of subsequent nucleotides of viral mRNA. The 2'-O-methylation performed by nsp16-nsp10 is crucial for the escape of the viral RNA from innate immunity. Inhibition of this enzymatic activity has been proposed as a way to combat coronaviruses. In this study, we employed X-ray crystallography to analyze the binding of the SAM analogues to the active site of nsp16-nsp10. We obtained eleven 3D crystal structures of the nsp16-nsp10 complexes with SAM-derived inhibitors, demonstrated different conformations of the methionine substituting part of the molecules, and confirmed that simultaneous dual-site targeting of both SAM and RNA sites correlates with higher inhibitory potential. PubMed: 39258386DOI: 10.1002/cmdc.202400618 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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