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

PDB-id
2mb3
Class
DNA-DNA inhibitor
Method
NMR
Summary
Solution structure of an intramolecular (3+1) human telomeric G-quadruplex bound to a telomestatin derivative
Reference
Chung, W.J., Heddi, B., Tera, M., Iida, K., Nagasawa, K., Phan, A.T.: (2013) "Solution structure of an intramolecular (3 + 1) human telomeric g-quadruplex bound to a telomestatin derivative." J.Am.Chem.Soc., 135, 13495-13501.
Abstract
Guanine-rich human telomeric DNA can adopt secondary structures known as G-quadruplexes, which can be targeted by small molecules to achieve anticancer effects. So far, the structural information on complexes between human telomeric DNA and ligands is limited to the parallel G-quadruplex conformation, despite the high structural polymorphism of human telomeric G-quadruplexes. No structure has been yet resolved for the complex with telomestatin, one of the most promising G-quadruplex-targeting anticancer drug candidates. Here we present the first high-resolution structure of the complex between an intramolecular (3 + 1) human telomeric G-quadruplex and a telomestatin derivative, the macrocyclic hexaoxazole L2H2-6M(2)OTD. This compound is observed to interact with the G-quadruplex through π-stacking and electrostatic interactions. This structural information provides a platform for the design of topology-specific G-quadruplex-targeting compounds and is valuable for the development of new potent anticancer drugs.
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 [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=ss-s groove=-wn- planarity=0.325 type=other  nts=4 GGGG A.DG3,A.DG9,A.DG17,A.DG21
 2 glyco-bond=--s- groove=-wn- planarity=0.314 type=other  nts=4 GGGG A.DG4,A.DG10,A.DG16,A.DG22
 3 glyco-bond=--s- groove=-wn- planarity=0.347 type=other  nts=4 GGGG A.DG5,A.DG11,A.DG15,A.DG23

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=ss-s groove=-wn- Major-->WC nts=4 GGGG A.DG3,A.DG9,A.DG17,A.DG21
 2  glyco-bond=--s- groove=-wn- WC-->Major nts=4 GGGG A.DG4,A.DG10,A.DG16,A.DG22
 3  glyco-bond=--s- groove=-wn- WC-->Major nts=4 GGGG A.DG5,A.DG11,A.DG15,A.DG23
  step#1  mm(<>,outward)  area=14.86 rise=3.81 twist=11.4
  step#2  pm(>>,forward)  area=12.41 rise=3.39 twist=24.7
  strand#1 DNA glyco-bond=s-- nts=3 GGG A.DG3,A.DG4,A.DG5
  strand#2 DNA glyco-bond=s-- nts=3 GGG A.DG9,A.DG10,A.DG11
  strand#3 DNA glyco-bond=-ss nts=3 GGG A.DG17,A.DG16,A.DG15
  strand#4 DNA glyco-bond=s-- nts=3 GGG A.DG21,A.DG22,A.DG23

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2 stacking diagrams
 1  glyco-bond=ss-s groove=-wn- Major-->WC nts=4 GGGG A.DG3,A.DG9,A.DG17,A.DG21
2 glyco-bond=--s- groove=-wn- WC-->Major nts=4 GGGG A.DG4,A.DG10,A.DG16,A.DG22
step#1 mm(<>,outward) area=14.86 rise=3.81 twist=11.4

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 2  glyco-bond=--s- groove=-wn- WC-->Major nts=4 GGGG A.DG4,A.DG10,A.DG16,A.DG22
3 glyco-bond=--s- groove=-wn- WC-->Major nts=4 GGGG A.DG5,A.DG11,A.DG15,A.DG23
step#2 pm(>>,forward) area=12.41 rise=3.39 twist=24.7

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

 1  glyco-bond=ss-s groove=-wn- Major-->WC nts=4 GGGG A.DG3,A.DG9,A.DG17,A.DG21
 2  glyco-bond=--s- groove=-wn- WC-->Major nts=4 GGGG A.DG4,A.DG10,A.DG16,A.DG22
 3  glyco-bond=--s- groove=-wn- WC-->Major nts=4 GGGG A.DG5,A.DG11,A.DG15,A.DG23
  step#1  mm(<>,outward)  area=14.86 rise=3.81 twist=11.4
  step#2  pm(>>,forward)  area=12.41 rise=3.39 twist=24.7
  strand#1  U DNA glyco-bond=s-- nts=3 GGG A.DG3,A.DG4,A.DG5
  strand#2  U DNA glyco-bond=s-- nts=3 GGG A.DG9,A.DG10,A.DG11
  strand#3  D DNA glyco-bond=-ss nts=3 GGG A.DG17,A.DG16,A.DG15
  strand#4  U DNA glyco-bond=s-- nts=3 GGG A.DG21,A.DG22,A.DG23
  loop#1 type=propeller strands=[#1,#2] nts=3 TTA A.DT6,A.DT7,A.DA8
  loop#2 type=lateral   strands=[#2,#3] nts=3 TTA A.DT12,A.DT13,A.DA14
  loop#3 type=lateral   strands=[#3,#4] nts=3 TTA A.DT18,A.DT19,A.DA20

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

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