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PDB-id
6h5r
Class
DNA
Method
X-ray (2.0 Å)
Summary
Structure of the complex of a human telomeric DNA with bis(1-butyl-3-methyl-imidazole-2-ylidene) gold(i)
Reference
Guarra, F., Marzo, T., Ferraroni, M., Papi, F., Bazzicalupi, C., Gratteri, P., Pescitelli, G., Messori, L., Biver, T., Gabbiani, C.: (2018) "Interaction of a gold(i) dicarbene anticancer drug with human telomeric DNA G-quadruplex: solution and computationally aided X-ray diffraction analysis." Dalton Trans, 47, 16132-16138.
Abstract
The bis carbene gold(i) complex [Au(1-butyl-3-methyl-2-ylidene)2]PF6, ([Au(NHC)2]PF6 hereafter), holds remarkable interest as a perspective anticancer agent. The compound is stable under physiological like conditions: its original structure is retained even in the presence of excess glutathione (GSH). Previous studies revealed its high cytotoxicity in vitro that correlates with the impairment of crucial metabolic and enzymatic cellular processes (Magherini et al., Oncotarget, 2018, 9, 28042). Here, the interaction of [Au(NHC)2]PF6 with the human telomeric DNA G-quadruplex Tel23 has been investigated in solution by means of high resolution mass spectrometry. ESI MS experiments well document the formation of stable 1 : 1 adducts between the biscarbene gold complex - in its intact form - and the DNA G-quadruplex Tel23. Next, through independent biophysical methods, we show that [Au(NHC)2]PF6 binding does not significantly affect the G quadruplex melting temperature nor its conformation. The crystal structure for the [Au(NHC)2]+/Tel24 adduct was eventually determined by a joint X-ray diffraction and in silico simulation approach. Through the careful integration of solution and solid-state data, a quite clear picture emerges for the interaction of this gold complex with the Tel23 G-quadruplex.
G4 notes
3 G-tetrads, 1 G4 helix, 1 G4 stem · 3(-P-P-P), parallel(4+0), UUUU

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

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

 1 glyco-bond=---- groove=---- planarity=0.036 type=planar nts=4 GGGG A.DG3,A.DG9,A.DG15,A.DG21
 2 glyco-bond=---- groove=---- planarity=0.031 type=planar nts=4 GGGG A.DG4,A.DG10,A.DG16,A.DG22
 3 glyco-bond=---- groove=---- planarity=0.203 type=bowl   nts=4 GGGG A.DG5,A.DG11,A.DG17,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=---- groove=---- WC-->Major nts=4 GGGG A.DG3,A.DG9,A.DG15,A.DG21
 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG4,A.DG10,A.DG16,A.DG22
 3  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG5,A.DG11,A.DG17,A.DG23
  step#1  pm(>>,forward)  area=8.27  rise=3.38 twist=34.2
  step#2  pm(>>,forward)  area=12.73 rise=3.46 twist=26.0
  strand#1 DNA glyco-bond=--- nts=3 GGG A.DG3,A.DG4,A.DG5
  strand#2 DNA glyco-bond=--- nts=3 GGG A.DG9,A.DG10,A.DG11
  strand#3 DNA glyco-bond=--- nts=3 GGG A.DG15,A.DG16,A.DG17
  strand#4 DNA glyco-bond=--- nts=3 GGG A.DG21,A.DG22,A.DG23

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2 stacking diagrams
 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG3,A.DG9,A.DG15,A.DG21
2 glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG4,A.DG10,A.DG16,A.DG22
step#1 pm(>>,forward) area=8.27 rise=3.38 twist=34.2

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 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG4,A.DG10,A.DG16,A.DG22
3 glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG5,A.DG11,A.DG17,A.DG23
step#2 pm(>>,forward) area=12.73 rise=3.46 twist=26.0

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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, UUUU, parallel, 3(-P-P-P), parallel(4+0)

 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG3,A.DG9,A.DG15,A.DG21
 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG4,A.DG10,A.DG16,A.DG22
 3  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.DG5,A.DG11,A.DG17,A.DG23
  step#1  pm(>>,forward)  area=8.27  rise=3.38 twist=34.2
  step#2  pm(>>,forward)  area=12.73 rise=3.46 twist=26.0
  strand#1  U DNA glyco-bond=--- nts=3 GGG A.DG3,A.DG4,A.DG5
  strand#2  U DNA glyco-bond=--- nts=3 GGG A.DG9,A.DG10,A.DG11
  strand#3  U DNA glyco-bond=--- nts=3 GGG A.DG15,A.DG16,A.DG17
  strand#4  U DNA glyco-bond=--- 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=propeller strands=[#2,#3] nts=3 TTA A.DT12,A.DT13,A.DA14
  loop#3 type=propeller 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)