Summary information and primary citation

PDB-id
9jx5
Class
DNA
Method
NMR
Summary
Solution NMR structure of the 1:1 complex of nop56 intronic g-quadruplex bound with pyridostatin
Reference
Yan Z, He A, Wan L, Gao Q, Jiang Y, Wang Y, Wang E, Li C, Yang Y, Li Y, Guo P, Han D (2025): "Structural Insights into an Antiparallel Chair-Type G-Quadruplex From the Intron of NOP56 Oncogene." Adv Sci, 12, e2406230. doi: 10.1002/advs.202406230.
Abstract
G-quadruplex (G4) structures play important roles in various biological processes, especially the gene regulation. Nucleolar protein 56 (NOP56) is an essential component in ribosome biogenesis while its overexpression associates with various types of cancers, rendering it a significant therapeutic target. Here for the first time, an antiparallel chair-type G4 structure formed by a 21-nt DNA sequence from the intron 1 of NOP56 is reported, and its high-resolution structure is determined using solution nuclear magnetic resonance spectroscopy. The NOP56-G4 has a special fold containing two G-tetrads and a C·G·C·G tetrad, which is further capped by a C∙C base pair. The G4 ligand pyridostatin (PDS) binds at the terminal G-tetrad through π-π stacking and electrostatic interactions, increasing the melting temperature of NOP56-G4 by ≈14 °C. This study further shows that PDS can significantly reduce NOP56 mRNA levels in three cancer cell lines. This work provides an unprecedented high-resolution structural basis for a special G4 structure from the intron of NOP56 and suggests a feasibility of targeting intronic G4 for gene regulation, propelling new avenues for G4 structure-based drug design and therapeutic strategy.
G4 notes
3 G-tetrads, 1 G4 helix, 1 G4 stem, UDUD, anti-parallel:chair, 2+2, 3(-Lw-Ln-Lw)

Cartoon-block schematics in six views (download the tarball)

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List of 3 G-tetrads

 1 glyco-bond=s-s- sugar=---- groove=wnwn planarity=0.241 type=saddle O- nts=4 GGGG A.DG2,A.DG9,A.DG14,A.DG21
 2 glyco-bond=-s-s sugar=---- groove=wnwn planarity=0.235 type=other  O+ nts=4 GGGG A.DG3,A.DG8,A.DG15,A.DG20
 3 glyco-bond=---- sugar=3--- groove=---- planarity=0.238 type=other  -- nts=4 CGCG A.DC4,A.DG7,A.DC16,A.DG19

List of 1 G4-helix

In DSSR, a G4-helix is defined by stacking interactions of G-tetrads, regardless of backbone connectivity, and may contain more than one G4-stem.

Helix#1, 3 G-tetrads, INTRA-molecular, with 1 stem
 1  glyco-bond=s-s- sugar=---- groove=wnwn Major-->WC O- nts=4 GGGG A.DG2,A.DG9,A.DG14,A.DG21
 2  glyco-bond=-s-s sugar=---- groove=wnwn WC-->Major O+ nts=4 GGGG A.DG3,A.DG8,A.DG15,A.DG20
 3  glyco-bond=---- sugar=3--- groove=----     --     -- nts=4 CGCG A.DC4,A.DG7,A.DC16,A.DG19
  step#1  mm(<>,outward)  area=20.85 rise=3.43 twist=11.4
  step#2  pm(>>,forward)  area=16.66 rise=3.23 twist=32.2
  strand#1 DNA glyco-bond=s-- sugar=--3 nts=3 GGC A.DG2,A.DG3,A.DC4
  strand#2 DNA glyco-bond=-s- sugar=--- nts=3 GGG A.DG9,A.DG8,A.DG7
  strand#3 DNA glyco-bond=s-- sugar=--- nts=3 GGC A.DG14,A.DG15,A.DC16
  strand#4 DNA glyco-bond=-s- sugar=--- nts=3 GGG A.DG21,A.DG20,A.DG19

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2 stacking diagrams 
 1  glyco-bond=s-s- sugar=---- groove=wnwn Major-->WC O- nts=4 GGGG A.DG2,A.DG9,A.DG14,A.DG21
 2  glyco-bond=-s-s sugar=---- groove=wnwn WC-->Major O+ nts=4 GGGG A.DG3,A.DG8,A.DG15,A.DG20
  step#1  mm(<>,outward)  area=20.85 rise=3.43 twist=11.4

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 2  glyco-bond=-s-s sugar=---- groove=wnwn WC-->Major O+ nts=4 GGGG A.DG3,A.DG8,A.DG15,A.DG20
 3  glyco-bond=---- sugar=3--- groove=----     --     -- nts=4 CGCG A.DC4,A.DG7,A.DC16,A.DG19
  step#2  pm(>>,forward)  area=16.66 rise=3.23 twist=32.2

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List of 1 G4-stem

In DSSR, a G4-stem is defined as a G4-helix with backbone connectivity. Bulges are also allowed along each of the four strands.

Stem#1, 3 G-tetrads, 3 loops, INTRA-molecular, UDUD, anti-parallel:chair, WARNING, 2+2, 3(-Lw-Ln-Lw), WARNING
 1  glyco-bond=s-s- sugar=---- groove=wnwn Major-->WC O- nts=4 GGGG A.DG2,A.DG9,A.DG14,A.DG21
 2  glyco-bond=-s-s sugar=---- groove=wnwn WC-->Major O+ nts=4 GGGG A.DG3,A.DG8,A.DG15,A.DG20
 3  glyco-bond=---- sugar=3--- groove=----     --     -- nts=4 CGCG A.DC4,A.DG7,A.DC16,A.DG19
  step#1  mm(<>,outward)  area=20.85 rise=3.43 twist=11.4
  step#2  pm(>>,forward)  area=16.66 rise=3.23 twist=32.2
  strand#1  U DNA glyco-bond=s-- sugar=--3 nts=3 GGC A.DG2,A.DG3,A.DC4
  strand#2  D DNA glyco-bond=-s- sugar=--- nts=3 GGG A.DG9,A.DG8,A.DG7
  strand#3  U DNA glyco-bond=s-- sugar=--- nts=3 GGC A.DG14,A.DG15,A.DC16
  strand#4  D DNA glyco-bond=-s- sugar=--- nts=3 GGG A.DG21,A.DG20,A.DG19
  loop#1 type=lateral   strands=[#1,#2] nts=2 CT A.DC5,A.DT6
  loop#2 type=lateral   strands=[#2,#3] nts=4 CCTG A.DC10,A.DC11,A.DT12,A.DG13
  loop#3 type=lateral   strands=[#3,#4] nts=2 CT A.DC17,A.DT18

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