Summary information and primary citation

PDB-id
8yu3
Class
DNA
Method
NMR
Summary
NMR solution structure of the 2:1 complex of a platinum(ii) compound bound to myc1234 g-quadruplex
Reference
Liu W, Zhu BC, Liu LY, Xia XY, Jang J, Dickerhoff J, Yang D, Mao ZW (2024): "Solution structures and effects of a platinum compound successively bound MYC G-quadruplex." Nucleic Acids Res., 52, 9397-9406. doi: 10.1093/nar/gkae649.
Abstract
G-quadruplex (G4) structures play integral roles in modulating biological functions and can be regulated by small molecules. The MYC gene is critical during tumor initiation and malignant progression, in which G4 acts as an important modulation motif. Herein, we reported the MYC promoter G4 recognized by a platinum(II) compound Pt-phen. Two Pt-phen-MYC G4 complex structures in 5 mM K+ were determined by NMR. The Pt-phen first strongly binds the 3'-end of MYC G4 to form a 1:1 3'-end binding complex and then binds 5'-end to form a 2:1 complex with more Pt-phen. In the complexes, the Pt-phen molecules are well-defined and stack over four bases at the G-tetrad for a highly extensive π-π interaction, with the Pt atom aligning with the center of the G-tetrad. The flanking residues were observed to rearrange and cover on top of Pt-phen to stabilize the whole complex. We further demonstrated that Pt-phen targets G4 DNA in living cells and represses MYC gene expression in cancer cells. Our work elucidated the structural basis of ligand binding to MYC promoter G4. The platinum compound bound G4 includes multiple complexes formation, providing insights into the design of metal ligands targeting oncogene G4 DNA.
G4 notes
3 G-tetrads, 1 G4 helix, 1 G4 stem, UUDU, hybrid1, 3+1, 3(-P-Lw-Ln)

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

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List of 3 G-tetrads

 1 glyco-bond=ss-s sugar=--3- groove=-wn- planarity=0.236 type=other  O- nts=4 GGGG A.DG3,A.DG7,A.DG14,A.DG16
 2 glyco-bond=--s- sugar=.... groove=-wn- planarity=0.228 type=other  O+ nts=4 GGGG A.DG4,A.DG8,A.DG13,A.DG17
 3 glyco-bond=--s- sugar=-.-3 groove=-wn- planarity=0.236 type=other  O+ nts=4 GGGG A.DG5,A.DG9,A.DG12,A.DG18

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=ss-s sugar=--3- groove=-wn- Major-->WC O- nts=4 GGGG A.DG3,A.DG7,A.DG14,A.DG16
 2  glyco-bond=--s- sugar=.... groove=-wn- WC-->Major O+ nts=4 GGGG A.DG4,A.DG8,A.DG13,A.DG17
 3  glyco-bond=--s- sugar=-.-3 groove=-wn- WC-->Major O+ nts=4 GGGG A.DG5,A.DG9,A.DG12,A.DG18
  step#1  mm(<>,outward)  area=12.17 rise=3.75 twist=19.5
  step#2  pm(>>,forward)  area=14.55 rise=3.49 twist=24.8
  strand#1 DNA glyco-bond=s-- sugar=-.- nts=3 GGG A.DG3,A.DG4,A.DG5
  strand#2 DNA glyco-bond=s-- sugar=-.. nts=3 GGG A.DG7,A.DG8,A.DG9
  strand#3 DNA glyco-bond=-ss sugar=3.- nts=3 GGG A.DG14,A.DG13,A.DG12
  strand#4 DNA glyco-bond=s-- sugar=-.3 nts=3 GGG A.DG16,A.DG17,A.DG18

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2 stacking diagrams 
 1  glyco-bond=ss-s sugar=--3- groove=-wn- Major-->WC O- nts=4 GGGG A.DG3,A.DG7,A.DG14,A.DG16
 2  glyco-bond=--s- sugar=.... groove=-wn- WC-->Major O+ nts=4 GGGG A.DG4,A.DG8,A.DG13,A.DG17
  step#1  mm(<>,outward)  area=12.17 rise=3.75 twist=19.5

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 2  glyco-bond=--s- sugar=.... groove=-wn- WC-->Major O+ nts=4 GGGG A.DG4,A.DG8,A.DG13,A.DG17
 3  glyco-bond=--s- sugar=-.-3 groove=-wn- WC-->Major O+ nts=4 GGGG A.DG5,A.DG9,A.DG12,A.DG18
  step#2  pm(>>,forward)  area=14.55 rise=3.49 twist=24.8

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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, UUDU, hybrid1, 3+1, 3(-P-Lw-Ln)
 1  glyco-bond=ss-s sugar=--3- groove=-wn- Major-->WC O- nts=4 GGGG A.DG3,A.DG7,A.DG14,A.DG16
 2  glyco-bond=--s- sugar=.... groove=-wn- WC-->Major O+ nts=4 GGGG A.DG4,A.DG8,A.DG13,A.DG17
 3  glyco-bond=--s- sugar=-.-3 groove=-wn- WC-->Major O+ nts=4 GGGG A.DG5,A.DG9,A.DG12,A.DG18
  step#1  mm(<>,outward)  area=12.17 rise=3.75 twist=19.5
  step#2  pm(>>,forward)  area=14.55 rise=3.49 twist=24.8
  strand#1  U DNA glyco-bond=s-- sugar=-.- nts=3 GGG A.DG3,A.DG4,A.DG5
  strand#2  U DNA glyco-bond=s-- sugar=-.. nts=3 GGG A.DG7,A.DG8,A.DG9
  strand#3  D DNA glyco-bond=-ss sugar=3.- nts=3 GGG A.DG14,A.DG13,A.DG12
  strand#4  U DNA glyco-bond=s-- sugar=-.3 nts=3 GGG A.DG16,A.DG17,A.DG18
  loop#1 type=propeller strands=[#1,#2] nts=1 A A.DA6
  loop#2 type=lateral   strands=[#2,#3] nts=2 TA A.DT10,A.DA11
  loop#3 type=lateral   strands=[#3,#4] nts=1 A A.DA15

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