3M3Y

RNA polymerase II elongation complex C

3M3Y の概要

• エントリーDOI: 10.2210/pdb3m3y/pdb
• 関連するPDBエントリー: 1R9T 1SFO 2E2H 3CO3 3M4O
• 分子名称: DNA-directed RNA polymerase II subunit RPB1, DNA-directed RNA polymerases I, II, and III subunit RPABC4, RNA (5'-R(*AP*UP*GP*GP*AP*GP*AP*GP*GP*AP*C)-3'), ... (16 entities in total)
• 機能のキーワード: transcription, mrna, multiprotein complex, molecular machine, dna, dna damage, cancer, platinum drug, dna-binding, dna-directed rna polymerase, isopeptide bond, magnesium, metal-binding, nucleotidyltransferase, nucleus, phosphoprotein, transferase, ubl conjugation, zinc, zinc-finger, polymorphism, cytoplasm, dna repair, transferase-dna-rna hybrid complex, transferase/dna-rna hybrid
• 由来する生物種: Saccharomyces cerevisiae (brewer's yeast,lager beer yeast,yeast); 詳細
• 細胞内の位置: Nucleus: P04050 P08518 P16370 P20434 P20436 P27999 P38902; Nucleus, nucleolus: P40422 P22139; Cytoplasm: P20435
• タンパク質・核酸の鎖数: 13
• 化学式量合計: 486859.72

構造登録者

Wang, D.,Zhu, G.,Huang, X.,Lippard, S.J. (登録日: 2010-03-10, 公開日: 2010-05-12, 最終更新日: 2023-09-06)

主引用文献

Wang, D.,Zhu, G.,Huang, X.,Lippard, S.J.
X-ray structure and mechanism of RNA polymerase II stalled at an antineoplastic monofunctional platinum-DNA adduct.
Proc.Natl.Acad.Sci.USA, 107:9584-9589, 2010

PubMed Abstract: DNA is a major target of anticancer drugs. The resulting adducts interfere with key cellular processes, such as transcription, to trigger downstream events responsible for drug activity. cis-Diammine(pyridine)chloroplatinum(II), cDPCP or pyriplatin, is a monofunctional platinum(II) analogue of the widely used anticancer drug cisplatin having significant anticancer properties with a different spectrum of activity. Its novel structure-activity properties hold promise for overcoming drug resistance and improving the spectrum of treatable cancers over those responsive to cisplatin. However, the detailed molecular mechanism by which cells process DNA modified by pyriplatin and related monofunctional complexes is not at all understood. Here we report the structure of a transcribing RNA polymerase II (pol II) complex stalled at a site-specific monofunctional pyriplatin-DNA adduct in the active site. The results reveal a molecular mechanism of pol II transcription inhibition and drug action that is dramatically different from transcription inhibition by cisplatin and UV-induced 1,2-intrastrand cross-links. Our findings provide insight into structure-activity relationships that may apply to the entire family of monofunctional DNA-damaging agents and pave the way for rational improvement of monofunctional platinum anticancer drugs.

PubMed: 20448203
DOI: 10.1073/pnas.1002565107

実験手法

X-RAY DIFFRACTION (3.18 Å)