8RZD の概要
| エントリーDOI | 10.2210/pdb8rzd/pdb |
| 分子名称 | 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) |
| 機能のキーワード | nsp16, nsp10, 2'-o-methyltransferase, viral protein |
| 由来する生物種 | Severe acute respiratory syndrome coronavirus 2 詳細 |
| タンパク質・核酸の鎖数 | 2 |
| 化学式量合計 | 49615.49 |
| 構造登録者 | |
| 主引用文献 | Kalnins, G.,Rudusa, L.,Bula, A.L.,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, 19: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 主引用文献が同じPDBエントリー |
| 実験手法 | X-RAY DIFFRACTION (2.1 Å) |
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