ArticleNature communications2022
Structural insight into the bulge-containing KRAS oncogene promoter G-quadruplex bound to berberine and coptisine.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 54 citations in OpenAlex.
- TRIM29-dependent AKR1B10 degradation ameliorates MASH.Science advances · 2026Article
- Structure-Informed Design of Distinct Parallel G-Quadruplex Stabilizers for KRAS-Driven Cancer Therapy.Angewandte Chemie (International ed. in English) · 2026Article
- Structural insights into the binding of CX-5461 and MTR-106 to G-quadruplex DNA.Nucleic acids research · 2026Article
- Modulating G-quadruplexes for therapeutic intervention: Structural diversity, stability, and emerging nucleic-acid-based strategies.Molecular therapy. Nucleic acids · 2026Review
- Molecular glue that stabilizes the LRPPRC-MET-G4 interaction complex to drive MET downregulation.Nature communications · 2026Article
- Precise discrimination of G-quadruplex conformation by chiral nanoassembly with photo-reversibility.Nature communications · 2026Article
- A small molecule disrupts G4-STAT1 interaction and synergizes with olaparib to drive cancer cell death.Nucleic acids research · 2026Article
- G-Quadruplex Unwinding Molecular Mechanisms by Helicases and Their Applications.International journal of molecular sciences · 2026Review
- Indirect identification of genomic G-quadruplexes via a small protein probe that specifically recognizes C-rich single-stranded DNA.Nucleic acids research · 2026Article
- Glutamic Acid-Chelated Cobalt Stabilizes G-Quadruplexes and Selectively Suppresses Hepatocellular Carcinoma Growth.Oncology research · 2026Article
- Natural G-Quadruplex Stabilizers: A Targeted Strategy for Breast Cancer Therapy.Drug design, development and therapy · 2026Review
- Thiazole peptidomimetics as chemical modulators ofRSC chemical biology · 2025Article
- Article
- The Relevance of G-Quadruplexes in Gene Promoters and the First Introns Associated with Transcriptional Regulation in Breast Cancer.International journal of molecular sciences · 2025Article
- DNA 5mC methylation inhibits the formation of G-quadruplex structures in the genome.Genome biology · 2025Article
- Perspectives on NcRNAs in HBV/cccDNA-driven HCC progression.Cancer cell international · 2025Review
- A DNP-Supported Solid-State NMR Approach to Study Nucleic Acids In Situ Reveals Berberine-Stabilized Hoogsteen Structures in Mitochondria.Angewandte Chemie (International ed. in English) · 2025Article
- Recent Progress and Potential of G4 Ligands in Cancer Immunotherapy.Molecules (Basel, Switzerland) · 2025Review
- Tandemly Repeated G-Quadruplex Structures in the Pseudorabies Virus Genome: Implications for Epiberberine-Based Antiviral Therapy.International journal of molecular sciences · 2025Article
- Structural Insights into an Antiparallel Chair-Type G-Quadruplex From the Intron of NOP56 Oncogene.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
KRAS is one of the most highly mutated oncoproteins, which is overexpressed in various human cancers and implicated in poor survival. The G-quadruplex formed in KRAS oncogene promoter (KRAS-G4) is a transcriptional modulator and amenable to small molecule targeting. However, no available KRAS-G4-ligand complex structure has yet been determined, which seriously hinders the structure-based rational design of KRAS-G4 targeting drugs. In this study, we report the NMR solution structures of a bulge-containing KRAS-G4 bound to berberine and coptisine, respectively. The determined complex structure shows a 2:1 binding stoichiometry with each compound recruiting the adjacent flacking adenine residue to form a "quasi-triad plane" that stacks over the two external G-tetrads. The binding involves both π-stacking and electrostatic interactions. Moreover, berberine and coptisine significantly lowered the KRAS mRNA levels in cancer cells. Our study thus provides molecular details of ligand interactions with KRAS-G4 and is beneficial for the design of specific KRAS-G4-interactive drugs.
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