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

PDB-id
5ccw
Class
drug-DNA
Method
X-ray (1.89 Å)
Summary
Structure of the complex of a human telomeric DNA with au(caffein-2-ylidene)2
Reference
Bazzicalupi, C., Ferraroni, M., Papi, F., Massai, L., Bertrand, B., Messori, L., Gratteri, P., Casini, A.: (2016) "Determinants for Tight and Selective Binding of a Medicinal Dicarbene Gold(I) Complex to a Telomeric DNA G-Quadruplex: a Joint ESI MS and XRD Investigation." Angew.Chem.Int.Ed.Engl., 55, 4256-4259.
Abstract
The dicarbene gold(I) complex [Au(9-methylcaffein-8-ylidene)2 ]BF4 is an exceptional organometallic compound of profound interest as a prospective anticancer agent. This gold(I) complex was previously reported to be highly cytotoxic toward various cancer cell lines in vitro and behaves as a selective G-quadruplex stabilizer. Interactions of the gold complex with various telomeric DNA models have been analyzed by a combined ESI MS and X-ray diffraction (XRD) approach. ESI MS measurements confirmed formation of stable adducts between the intact gold(I) complex and Tel 23 DNA sequence. The crystal structure of the adduct formed between [Au(9-methylcaffein-8-ylidene)2 ](+) and Tel 23 DNA G-quadruplex was solved. Tel 23 maintains a characteristic propeller conformation while binding three gold(I) dicarbene moieties at two distinct sites. Stacking interactions appear to drive noncovalent binding of the gold(I) complex. The structural basis for tight gold(I) complex/G-quadruplex recognition and its selectivity are described.
G4 notes
3 G-tetrads, 1 G4 helix, 1 G4 stem · 3(-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=0.225 type=bowl-2 nts=4 GGGG A.DG3,A.DG9,A.DG15,A.DG21
 2 glyco-bond=---- groove=---- planarity=0.223 type=bowl-2 nts=4 GGGG A.DG4,A.DG10,A.DG16,A.DG22
 3 glyco-bond=---- groove=---- planarity=0.313 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=9.41  rise=3.30 twist=30.4
  step#2  pm(>>,forward)  area=12.55 rise=3.44 twist=26.7
  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=9.41 rise=3.30 twist=30.4

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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=12.55 rise=3.44 twist=26.7

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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, 2 loops, INTRA-molecular, UUUU, parallel, 3(-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=9.41  rise=3.30 twist=30.4
  step#2  pm(>>,forward)  area=12.55 rise=3.44 twist=26.7
  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=[#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)