DSSR-enabled G4 identification/annotation: PDB entry 7pnl
Summary information and primary citation
- PDB-id
- 7pnl
- Class
- DNA
- Method
- X-ray (1.83 Å)
- Summary
- Complex between monomolecular human telomeric g-quadruplex and a sulfonamide derivative of the natural alkaloid berberine
- Reference
- Nocentini A, Di Porzio A, Bonardi A, Bazzicalupi C, Petreni A, Biver T, Bua S, Marzano S, Amato J, Pagano B, Iaccarino N, De Tito S, Amente S, Supuran CT, Randazzo A, Gratteri P (2024): "Development of a multi-targeted chemotherapeutic approach based on G-quadruplex stabilisation and carbonic anhydrase inhibition." J Enzyme Inhib Med Chem, 39, 2366236. doi: 10.1080/14756366.2024.2366236.
- Abstract
- A novel class of compounds designed to hit two anti-tumour targets, G-quadruplex structures and human carbonic anhydrases (hCAs) IX and XII is proposed. The induction/stabilisation of G-quadruplex structures by small molecules has emerged as an anticancer strategy, disrupting telomere maintenance and reducing oncogene expression. hCAs IX and XII are well-established anti-tumour targets, upregulated in many hypoxic tumours and contributing to metastasis. The ligands reported feature a berberine G-quadruplex stabiliser scaffold connected to a moiety inhibiting hCAs IX and XII. <i>In vitro</i> experiments showed that our compounds selectively stabilise G-quadruplex structures and inhibit hCAs IX and XII. The crystal structure of a telomeric G-quadruplex in complex with one of these ligands was obtained, shedding light on the ligand/target interaction mode. The most promising ligands showed significant cytotoxicity against CA IX-positive HeLa cancer cells in hypoxia, and the ability to stabilise G-quadruplexes within tumour cells.
- G4 notes
- 3 G-tetrads, 1 G4 helix, 1 G4 stem, UUUU, parallel, 4+0, 3(-P-P-P)
Cartoon-block schematics in six views (download the tarball)
List of 3 G-tetrads
1 glyco-bond=---- sugar=---- groove=---- planarity=0.055 type=planar O+ nts=4 GGGG A.DG2,A.DG8,A.DG14,A.DG20 2 glyco-bond=---- sugar=---- groove=---- planarity=0.037 type=planar O+ nts=4 GGGG A.DG3,A.DG9,A.DG15,A.DG21 3 glyco-bond=---- sugar=---- groove=---- planarity=0.153 type=planar O+ nts=4 GGGG A.DG4,A.DG10,A.DG16,A.DG22
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-tetrads, INTRA-molecular, with 1 stem
|
1 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG2,A.DG8,A.DG14,A.DG20 2 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG3,A.DG9,A.DG15,A.DG21 3 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG4,A.DG10,A.DG16,A.DG22 step#1 pm(>>,forward) area=8.77 rise=3.31 twist=34.6 step#2 pm(>>,forward) area=13.42 rise=3.45 twist=25.8 strand#1 DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG2,A.DG3,A.DG4 strand#2 DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG8,A.DG9,A.DG10 strand#3 DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG14,A.DG15,A.DG16 strand#4 DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG20,A.DG21,A.DG22 |
| 2 stacking diagrams | |
|
1 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG2,A.DG8,A.DG14,A.DG20 |
|
2 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG3,A.DG9,A.DG15,A.DG21 |
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-tetrads, 3 loops, INTRA-molecular, UUUU, parallel, 4+0, 3(-P-P-P)
|
1 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG2,A.DG8,A.DG14,A.DG20 2 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG3,A.DG9,A.DG15,A.DG21 3 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG4,A.DG10,A.DG16,A.DG22 step#1 pm(>>,forward) area=8.77 rise=3.31 twist=34.6 step#2 pm(>>,forward) area=13.42 rise=3.45 twist=25.8 strand#1 U DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG2,A.DG3,A.DG4 strand#2 U DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG8,A.DG9,A.DG10 strand#3 U DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG14,A.DG15,A.DG16 strand#4 U DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG20,A.DG21,A.DG22 loop#1 type=propeller strands=[#1,#2] nts=3 TTA A.DT5,A.DT6,A.DA7 loop#2 type=propeller strands=[#2,#3] nts=3 TTA A.DT11,A.DT12,A.DA13 loop#3 type=propeller strands=[#3,#4] nts=3 TTA A.DT17,A.DT18,A.DA19 |