Summary information [schematics · tetrads · helices · stems · costacks · homepage]

PDB-id
5mvb
Class
DNA
Method
NMR
Summary
Solution structure of a human G-quadruplex hybrid-2 form in complex with a gold-ligand
Reference
Wirmer-Bartoschek, J., Bendel, L.E., Jonker, H.R.A., Grun, J.T., Papi, F., Bazzicalupi, C., Messori, L., Gratteri, P., Schwalbe, H.: (2017) "Solution NMR Structure of a Ligand/Hybrid-2-G-Quadruplex Complex Reveals Rearrangements that Affect Ligand Binding." Angew. Chem. Int. Ed. Engl., 56, 7102-7106.
Abstract
Telomeric G-quadruplexes have recently emerged as drug targets in cancer research. Herein, we present the first NMR structure of a telomeric DNA G-quadruplex that adopts the biologically relevant hybrid-2 conformation in a ligand-bound state. We solved the complex with a metalorganic gold(III) ligand that stabilizes G-quadruplexes. Analysis of the free and bound structures reveals structural changes in the capping region of the G-quadruplex. The ligand is sandwiched between one terminal G-tetrad and a flanking nucleotide. This complex structure involves a major structural rearrangement compared to the free G-quadruplex structure as observed for other G-quadruplexes in different conformations, invalidating simple docking approaches to ligand-G-quadruplex structure determination.
G4 notes
3 G-tetrads, 1 G4 helix, 1 G4 stem · 3(-Lw-Ln-P), hybrid-2(3+1), UDUU

Base-block schematics in six views [summary · tetrads · helices · stems · costacks · homepage]

PyMOL session file PDB file View in 3Dmol.js

List of 3 G-tetrads [summary · schematics · helices · stems · costacks · homepage]

 1 glyco-bond=s-ss groove=wn-- planarity=0.348 type=bowl   nts=4 GGGG A.DG4,A.DG12,A.DG16,A.DG22
 2 glyco-bond=-s-- groove=wn-- planarity=0.211 type=other  nts=4 GGGG A.DG5,A.DG11,A.DG17,A.DG23
 3 glyco-bond=-s-- groove=wn-- planarity=0.307 type=bowl   nts=4 GGGG A.DG6,A.DG10,A.DG18,A.DG24

List of 1 G4-helix [summary · schematics · tetrads · stems · costacks · homepage]

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=s-ss groove=wn-- Major-->WC nts=4 GGGG A.DG4,A.DG12,A.DG16,A.DG22
 2  glyco-bond=-s-- groove=wn-- WC-->Major nts=4 GGGG A.DG5,A.DG11,A.DG17,A.DG23
 3  glyco-bond=-s-- groove=wn-- WC-->Major nts=4 GGGG A.DG6,A.DG10,A.DG18,A.DG24
  step#1  mm(<>,outward)  area=14.78 rise=3.80 twist=11.8
  step#2  pm(>>,forward)  area=11.80 rise=3.91 twist=25.0
  strand#1 DNA glyco-bond=s-- nts=3 GGG A.DG4,A.DG5,A.DG6
  strand#2 DNA glyco-bond=-ss nts=3 GGG A.DG12,A.DG11,A.DG10
  strand#3 DNA glyco-bond=s-- nts=3 GGG A.DG16,A.DG17,A.DG18
  strand#4 DNA glyco-bond=s-- nts=3 GGG A.DG22,A.DG23,A.DG24

Download PDB file
Interactive view in 3Dmol.js

2 stacking diagrams
 1  glyco-bond=s-ss groove=wn-- Major-->WC nts=4 GGGG A.DG4,A.DG12,A.DG16,A.DG22
2 glyco-bond=-s-- groove=wn-- WC-->Major nts=4 GGGG A.DG5,A.DG11,A.DG17,A.DG23
step#1 mm(<>,outward) area=14.78 rise=3.80 twist=11.8

Download PDB file
Interactive view in 3Dmol.js

 2  glyco-bond=-s-- groove=wn-- WC-->Major nts=4 GGGG A.DG5,A.DG11,A.DG17,A.DG23
3 glyco-bond=-s-- groove=wn-- WC-->Major nts=4 GGGG A.DG6,A.DG10,A.DG18,A.DG24
step#2 pm(>>,forward) area=11.80 rise=3.91 twist=25.0

Download PDB file
Interactive view in 3Dmol.js

List of 1 G4-stem [summary · schematics · tetrads · helices · costacks · homepage]

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, UDUU, anti-parallel, 3(-Lw-Ln-P), hybrid-2(3+1)

 1  glyco-bond=s-ss groove=wn-- Major-->WC nts=4 GGGG A.DG4,A.DG12,A.DG16,A.DG22
 2  glyco-bond=-s-- groove=wn-- WC-->Major nts=4 GGGG A.DG5,A.DG11,A.DG17,A.DG23
 3  glyco-bond=-s-- groove=wn-- WC-->Major nts=4 GGGG A.DG6,A.DG10,A.DG18,A.DG24
  step#1  mm(<>,outward)  area=14.78 rise=3.80 twist=11.8
  step#2  pm(>>,forward)  area=11.80 rise=3.91 twist=25.0
  strand#1  U DNA glyco-bond=s-- nts=3 GGG A.DG4,A.DG5,A.DG6
  strand#2  D DNA glyco-bond=-ss nts=3 GGG A.DG12,A.DG11,A.DG10
  strand#3  U DNA glyco-bond=s-- nts=3 GGG A.DG16,A.DG17,A.DG18
  strand#4  U DNA glyco-bond=s-- nts=3 GGG A.DG22,A.DG23,A.DG24
  loop#1 type=lateral   strands=[#1,#2] nts=3 TTA A.DT7,A.DT8,A.DA9
  loop#2 type=lateral   strands=[#2,#3] nts=3 TTA A.DT13,A.DT14,A.DA15
  loop#3 type=propeller strands=[#3,#4] nts=3 TTA A.DT19,A.DT20,A.DA21

Download PDB file
Interactive view in 3Dmol.js

List of 0 G4 coaxial stacks [summary · schematics · tetrads · helices · stems · homepage]

List of 0 non-stem G4-loops (including the two closing Gs)