Summary information

PDB id
7djv
Class
DNA
Method
NMR
Summary
NMR solution structure of the 2:1 complex of a platinum(ii) compound bound to myc1234 g-quadruplex reveals the mechanism of conformational switch and dynamic binding of g-quadruplex
Reference
Liu W, Zhu BC, Liu LY, Xia XY, Mao ZW (2022): "G-quadruplex structural transition driven by a platinum compound." Nucleic Acids Res., 50, 7816-7828. doi: 10.1093/nar/gkac572.
Abstract
G-quadruplex (G4) transitions play integral roles in regulating biological functions and can be modified by ligands. However, little is known about G4 transitions. Herein, we reveal distinct pathways of a platinum(II) compound Pt-phen converting parallel-stranded MYC G4 to a hybrid-type structure. Three NMR structures, 1:1 5'-end binding, 1:1 3'-end binding and 2:1 Pt-phen-MYC G4 complexes, were determined by NMR. We find that Pt-phen drives G4 transition at a low ratio. Under physiological 100 mM K+ conditions, a significant stable hydrogen-bonded T:T:A triad is formed at 3'-end of hybrid-type Myc1234, and consequently, Pt-phen first binds the 5'-end to form a 1:1 5'-end binding complex and then disrupts the 3' T:T:A triad and binds 3'-end to form a 2:1 complex with more Pt-phen. Remarkably, the G4 transition pathway is different in 5 mM K+ with Pt-phen first binding the 3'-end and then the 5'-end. 'Edgewise-loop and flanking/ligand/G-tetrad' sandwich structure formation and terminal T:T:A triad stabilization play decisive roles in advancing and altering transition pathways. Our work is the first to elucidate the molecular structures of G4 transitions driven by a small molecule. The ligand-driven G4 transition is a dynamic process that includes a quick G4 transition and multiple complexes formation.
G4 notes
3 G-tetrads, 1 G4 helix, 1 G4 stem, 3(-P-Lw-Ln), hybrid-1(3+1), UUDU

Base-block schematics in six views

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List of 3 G-tetrads

 1 glyco-bond=ss-s sugar=--3- groove=-wn- planarity=0.236 type=other  nts=4 GGGG A.DG3,A.DG7,A.DG14,A.DG16
 2 glyco-bond=--s- sugar=.... groove=-wn- planarity=0.228 type=other  nts=4 GGGG A.DG4,A.DG8,A.DG13,A.DG17
 3 glyco-bond=--s- sugar=-.-3 groove=-wn- planarity=0.236 type=other  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-tetrad layers, INTRA-molecular, with 1 stem

 1  glyco-bond=ss-s sugar=--3- groove=-wn- Major-->WC nts=4 GGGG A.DG3,A.DG7,A.DG14,A.DG16
 2  glyco-bond=--s- sugar=.... groove=-wn- WC-->Major nts=4 GGGG A.DG4,A.DG8,A.DG13,A.DG17
 3  glyco-bond=--s- sugar=-.-3 groove=-wn- WC-->Major 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 nts=4 GGGG A.DG3,A.DG7,A.DG14,A.DG16
2 glyco-bond=--s- sugar=.... groove=-wn- WC-->Major 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 nts=4 GGGG A.DG4,A.DG8,A.DG13,A.DG17
3 glyco-bond=--s- sugar=-.-3 groove=-wn- WC-->Major 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-tetrad layers, 3 loops, INTRA-molecular, UUDU, hybrid-(mixed), 3(-P-Lw-Ln), hybrid-1(3+1)

 1  glyco-bond=ss-s sugar=--3- groove=-wn- Major-->WC nts=4 GGGG A.DG3,A.DG7,A.DG14,A.DG16
 2  glyco-bond=--s- sugar=.... groove=-wn- WC-->Major nts=4 GGGG A.DG4,A.DG8,A.DG13,A.DG17
 3  glyco-bond=--s- sugar=-.-3 groove=-wn- WC-->Major 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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