DSSR-enabled G4 identification/annotation: PDB entry 6h5r
Summary information and primary citation
- 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. doi: 10.1039/c8dt03607a.
- 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
- 6 G-tetrads, 1 G4 helix, 2 G4 stems, 1 G4 coaxial stack, UUUU, parallel, 4+0, 3(-P-P-P), coaxial interfaces: 5'/5'
Cartoon-block schematics in six views (download the tarball)
List of 6 G-tetrads
1 glyco-bond=---- sugar=---- groove=---- planarity=0.036 type=planar O+ nts=4 GGGG 1:A.DG3,1:A.DG9,1:A.DG15,1:A.DG21 2 glyco-bond=---- sugar=---- groove=---- planarity=0.031 type=planar O+ nts=4 GGGG 1:A.DG4,1:A.DG10,1:A.DG16,1:A.DG22 3 glyco-bond=---- sugar=---- groove=---- planarity=0.203 type=bowl O+ nts=4 GGGG 1:A.DG5,1:A.DG11,1:A.DG17,1:A.DG23 4 glyco-bond=---- sugar=---- groove=---- planarity=0.036 type=planar O+ nts=4 GGGG 2:A.DG3,2:A.DG9,2:A.DG15,2:A.DG21 5 glyco-bond=---- sugar=---- groove=---- planarity=0.031 type=planar O+ nts=4 GGGG 2:A.DG4,2:A.DG10,2:A.DG16,2:A.DG22 6 glyco-bond=---- sugar=---- groove=---- planarity=0.203 type=bowl O+ nts=4 GGGG 2:A.DG5,2:A.DG11,2:A.DG17,2:A.DG23
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, 6 G-tetrads, inter-molecular, with 2 stems
|
1 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG 1:A.DG5,1:A.DG11,1:A.DG17,1:A.DG23 2 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG 1:A.DG4,1:A.DG10,1:A.DG16,1:A.DG22 3* glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG 1:A.DG3,1:A.DG9,1:A.DG15,1:A.DG21 4 glyco-bond=---- sugar=---- groove=---- Major-->WC O+ nts=4 GGGG 2:A.DG15,2:A.DG9,2:A.DG3,2:A.DG21 5 glyco-bond=---- sugar=---- groove=---- Major-->WC O+ nts=4 GGGG 2:A.DG16,2:A.DG10,2:A.DG4,2:A.DG22 6 glyco-bond=---- sugar=---- groove=---- Major-->WC O+ nts=4 GGGG 2:A.DG17,2:A.DG11,2:A.DG5,2:A.DG23 step#1 mp(<<,backward) area=12.73 rise=3.46 twist=26.0 step#2 mp(<<,backward) area=8.27 rise=3.38 twist=34.2 step#3 mm(<>,outward) area=29.25 rise=3.34 twist=-10.4 step#4 pm(>>,forward) area=8.27 rise=3.38 twist=34.2 step#5 pm(>>,forward) area=12.73 rise=3.46 twist=26.0 strand#1 DNA glyco-bond=------ sugar=------ nts=6 GGGGGG 1:A.DG5,1:A.DG4,1:A.DG3,2:A.DG15,2:A.DG16,2:A.DG17 strand#2 DNA glyco-bond=------ sugar=------ nts=6 GGGGGG 1:A.DG11,1:A.DG10,1:A.DG9,2:A.DG9,2:A.DG10,2:A.DG11 strand#3 DNA glyco-bond=------ sugar=------ nts=6 GGGGGG 1:A.DG17,1:A.DG16,1:A.DG15,2:A.DG3,2:A.DG4,2:A.DG5 strand#4 DNA glyco-bond=------ sugar=------ nts=6 GGGGGG 1:A.DG23,1:A.DG22,1:A.DG21,2:A.DG21,2:A.DG22,2:A.DG23 |
| 5 stacking diagrams | |
|
1 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG 1:A.DG5,1:A.DG11,1:A.DG17,1:A.DG23 |
|
2 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG 1:A.DG4,1:A.DG10,1:A.DG16,1:A.DG22 |
|
3* glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG 1:A.DG3,1:A.DG9,1:A.DG15,1:A.DG21 |
|
4 glyco-bond=---- sugar=---- groove=---- Major-->WC O+ nts=4 GGGG 2:A.DG15,2:A.DG9,2:A.DG3,2:A.DG21 |
|
5 glyco-bond=---- sugar=---- groove=---- Major-->WC O+ nts=4 GGGG 2:A.DG16,2:A.DG10,2:A.DG4,2:A.DG22 |
List of 2 G4-stems
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, UUUU, parallel, 4+0, 3(-P-P-P)
|
1 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG 1:A.DG3,1:A.DG9,1:A.DG15,1:A.DG21 2 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG 1:A.DG4,1:A.DG10,1:A.DG16,1:A.DG22 3 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG 1:A.DG5,1:A.DG11,1:A.DG17,1: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=--- sugar=--- nts=3 GGG 1:A.DG3,1:A.DG4,1:A.DG5 strand#2 U DNA glyco-bond=--- sugar=--- nts=3 GGG 1:A.DG9,1:A.DG10,1:A.DG11 strand#3 U DNA glyco-bond=--- sugar=--- nts=3 GGG 1:A.DG15,1:A.DG16,1:A.DG17 strand#4 U DNA glyco-bond=--- sugar=--- nts=3 GGG 1:A.DG21,1:A.DG22,1:A.DG23 loop#1 type=propeller strands=[#1,#2] nts=3 TTA 1:A.DT6,1:A.DT7,1:A.DA8 loop#2 type=propeller strands=[#2,#3] nts=3 TTA 1:A.DT12,1:A.DT13,1:A.DA14 loop#3 type=propeller strands=[#3,#4] nts=3 TTA 1:A.DT18,1:A.DT19,1:A.DA20 |
Stem#2, 3 G-tetrads, 3 loops, INTRA-molecular, UUUU, parallel, 4+0, 3(-P-P-P)
|
1 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG 2:A.DG3,2:A.DG9,2:A.DG15,2:A.DG21 2 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG 2:A.DG4,2:A.DG10,2:A.DG16,2:A.DG22 3 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG 2:A.DG5,2:A.DG11,2:A.DG17,2: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=--- sugar=--- nts=3 GGG 2:A.DG3,2:A.DG4,2:A.DG5 strand#2 U DNA glyco-bond=--- sugar=--- nts=3 GGG 2:A.DG9,2:A.DG10,2:A.DG11 strand#3 U DNA glyco-bond=--- sugar=--- nts=3 GGG 2:A.DG15,2:A.DG16,2:A.DG17 strand#4 U DNA glyco-bond=--- sugar=--- nts=3 GGG 2:A.DG21,2:A.DG22,2:A.DG23 loop#1 type=propeller strands=[#1,#2] nts=3 TTA 2:A.DT6,2:A.DT7,2:A.DA8 loop#2 type=propeller strands=[#2,#3] nts=3 TTA 2:A.DT12,2:A.DT13,2:A.DA14 loop#3 type=propeller strands=[#3,#4] nts=3 TTA 2:A.DT18,2:A.DT19,2:A.DA20 |
List of 1 G4 coaxial stack
1 G4 helix#1 contains 2 G4 stems: [#1,#2] [5'/5']