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

PDB-id
5mjx
Class
DNA
Method
NMR
Summary
2'f-ana-DNA chimeric tba quadruplex structure
Reference
Lietard, J., Abou Assi, H., Gomez-Pinto, I., Gonzalez, C., Somoza, M.M., Damha, M.J.: (2017) "Mapping the affinity landscape of Thrombin-binding aptamers on 2 F-ANA/DNA chimeric G-Quadruplex microarrays." Nucleic Acids Res., 45, 1619-1632.
Abstract
In situ fabricated nucleic acids microarrays are versatile and very high-throughput platforms for aptamer optimization and discovery, but the chemical space that can be probed against a given target has largely been confined to DNA, while RNA and non-natural nucleic acid microarrays are still an essentially uncharted territory. 2΄-Fluoroarabinonucleic acid (2΄F-ANA) is a prime candidate for such use in microarrays. Indeed, 2΄F-ANA chemistry is readily amenable to photolithographic microarray synthesis and its potential in high affinity aptamers has been recently discovered. We thus synthesized the first microarrays containing 2΄F-ANA and 2΄F-ANA/DNA chimeric sequences to fully map the binding affinity landscape of the TBA1 thrombin-binding G-quadruplex aptamer containing all 32 768 possible DNA-to-2΄F-ANA mutations. The resulting microarray was screened against thrombin to identify a series of promising 2΄F-ANA-modified aptamer candidates with Kds significantly lower than that of the unmodified control and which were found to adopt highly stable, antiparallel-folded G-quadruplex structures. The solution structure of the TBA1 aptamer modified with 2΄F-ANA at position T3 shows that fluorine substitution preorganizes the dinucleotide loop into the proper conformation for interaction with thrombin. Overall, our work strengthens the potential of 2΄F-ANA in aptamer research and further expands non-genomic applications of nucleic acids microarrays.
G4 notes
2 G-tetrads, 1 G4 helix, 1 G4 stem · 2(+Ln+Lw+Ln), chair(2+2), UDUD

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

PyMOL session file PDB file View in 3Dmol.js

List of 2 G-tetrads [summary · schematics · helices · stems · costacks · homepage]

 1 glyco-bond=s-s- groove=wnwn planarity=0.198 type=other  nts=4 GGGG A.DG1,A.DG15,A.DG10,A.DG6
 2 glyco-bond=-s-s groove=wnwn planarity=0.254 type=bowl   nts=4 GGGG A.DG2,A.DG14,A.DG11,A.DG5

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, 2 G-tetrad layers, INTRA-molecular, with 1 stem

 1  glyco-bond=s-s- groove=wnwn Major-->WC nts=4 GGGG A.DG1,A.DG15,A.DG10,A.DG6
 2  glyco-bond=-s-s groove=wnwn WC-->Major nts=4 GGGG A.DG2,A.DG14,A.DG11,A.DG5
  step#1  mm(<>,outward)  area=18.13 rise=3.51 twist=17.9
  strand#1 DNA glyco-bond=s- nts=2 GG A.DG1,A.DG2
  strand#2 DNA glyco-bond=-s nts=2 GG A.DG15,A.DG14
  strand#3 DNA glyco-bond=s- nts=2 GG A.DG10,A.DG11
  strand#4 DNA glyco-bond=-s nts=2 GG A.DG6,A.DG5

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1 stacking diagram
 1  glyco-bond=s-s- groove=wnwn Major-->WC nts=4 GGGG A.DG1,A.DG15,A.DG10,A.DG6
2 glyco-bond=-s-s groove=wnwn WC-->Major nts=4 GGGG A.DG2,A.DG14,A.DG11,A.DG5
step#1 mm(<>,outward) area=18.13 rise=3.51 twist=17.9

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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, 2 G-tetrad layers, 3 loops, INTRA-molecular, UDUD, anti-parallel, 2(+Ln+Lw+Ln), chair(2+2)

 1  glyco-bond=s-s- groove=wnwn Major-->WC nts=4 GGGG A.DG1,A.DG15,A.DG10,A.DG6
 2  glyco-bond=-s-s groove=wnwn WC-->Major nts=4 GGGG A.DG2,A.DG14,A.DG11,A.DG5
  step#1  mm(<>,outward)  area=18.13 rise=3.51 twist=17.9
  strand#1  U DNA glyco-bond=s- nts=2 GG A.DG1,A.DG2
  strand#2  D DNA glyco-bond=-s nts=2 GG A.DG15,A.DG14
  strand#3  U DNA glyco-bond=s- nts=2 GG A.DG10,A.DG11
  strand#4  D DNA glyco-bond=-s nts=2 GG A.DG6,A.DG5
  loop#1 type=lateral   strands=[#1,#4] nts=2 tT A.TAF3,A.DT4
  loop#2 type=lateral   strands=[#4,#3] nts=3 TGT A.DT7,A.DG8,A.DT9
  loop#3 type=lateral   strands=[#3,#2] nts=2 TT A.DT12,A.DT13

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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)