EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	The herpes simplex origin-binding protein: mechanisms for sequence-specific DNA binding and dimerization revealed by Cryo-EM.
ジャーナル・号・ページ	Nucleic Acids Res, Vol. 53, Issue 19, Year 2025
掲載日	2025年10月14日
著者	Emil Gustavsson / Kay Grünewald / Per Elias / B Martin Hällberg /
PubMed 要旨	Herpes simplex viruses 1 and 2 (HSV-1,2) present growing treatment challenges due to increasing resistance to antivirals targeting viral DNA polymerase, particularly in immunocompromised individuals. ...Herpes simplex viruses 1 and 2 (HSV-1,2) present growing treatment challenges due to increasing resistance to antivirals targeting viral DNA polymerase, particularly in immunocompromised individuals. The HSV-1 origin-binding protein (OBP), an essential Superfamily 2 (SF2) DNA helicase encoded by the UL9 gene, is a promising alternative therapeutic target. Here, we present cryo-EM structures of OBP at up to 2.8 Å resolution in multiple conformational states, including complexes with the OriS recognition sequence and the non-hydrolyzable ATP analog ATPγS. The structures reveal an unexpected head-to-tail dimer stabilized by the C-terminal domain, where the conserved RVKNL motif mediates sequence-specific DNA recognition. The C-terminal domain extends into the partner monomer, suggesting a regulatory mechanism involving the single-stranded DNA-binding protein ICP8. We also resolve an OBP monomer bound to a DNA hairpin with a 3' single-stranded tail (mini-OriS), and at lower resolution, a dimer-dimer assembly of two OBP dimers bound simultaneously to OriS or mini-OriS. These structures uncover the molecular basis of HSV-1 origin recognition and unwinding, and identify multiple druggable interfaces, laying the groundwork for structure-based antiviral development targeting HSV-1 OBP.
リンク	Nucleic Acids Res / PubMed:41125242 / PubMed Central
手法	EM (単粒子)
解像度	2.74 - 4.38 Å
構造データ	52135 9hgi EMDB-52135, PDB-9hgi: HSV-1 Origin Binding Protein in complex with double-stranded DNA recognition sequence OriS with 6 basepairs removed from the AT-rich region 手法: EM (単粒子) / 解像度: 2.77 Å EMDB-52136: Focused map of HSV-1 Origin Binding Protein monomer A in complex with double-stranded DNA recognition sequence OriS with 6 basepairs removed from the AT-rich region 手法: EM (単粒子) / 解像度: 2.76 Å EMDB-52137: Focused map of HSV-1 Origin Binding Protein monomer B in complex with double-stranded DNA recognition sequence OriS with 6 basepairs removed from the AT-rich region 手法: EM (単粒子) / 解像度: 2.74 Å 52145 9hgj EMDB-52145, PDB-9hgj: HSV-1 Origin Binding Protein in complex with double-stranded DNA recognition sequence OriS and non-hydrolyzable ATP analog 手法: EM (単粒子) / 解像度: 3.53 Å EMDB-52146: Composite map of HSV-1 Origin Binding Protein tetramer in complex with single-stranded DNA recognition sites Box 1 and Box 3 with 10 dT-tail 手法: EM (単粒子) / 解像度: 4.34 Å EMDB-52147: Consensus map of HSV-1 Origin Binding Protein tetramer in complex with single-stranded DNA recognition sites Box 1 and Box 3 with 10 dT-tail 手法: EM (単粒子) / 解像度: 4.34 Å EMDB-52148: Focused map of dimer 1 in HSV-1 Origin Binding Protein tetramer in complex with single-stranded DNA recognition sites Box 1 and Box 3 with 10 dT-tail 手法: EM (単粒子) / 解像度: 4.38 Å EMDB-52149: Focused map of dimer 2 of HSV-1 Origin Binding Protein tetramer in complex with single-stranded DNA recognition sites Box 1 and Box 3 with 10 dT-tail 手法: EM (単粒子) / 解像度: 4.17 Å EMDB-52150: HSV-1 Origin Binding Protein monomer in complex with hairpin DNA OriS recognition sites Box 1 and Box 3 with 10 dT-tail 手法: EM (単粒子) / 解像度: 2.9 Å
化合物	ChemComp-AGS: PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER / ATP-γ-S / ATP-gamma-S, エネルギー貯蔵分子類似体YM ChemComp-MG*: Unknown entry / マグネシウムジカチオン
由来	human alphaherpesvirus 1 strain kos (ヘルペスウイルス) synthetic construct (人工物)
キーワード	DNA BINDING PROTEIN / DNA / Helicase / Complex