Summary information

PDB id
1y8d
Class
DNA
Method
NMR
Summary
Dimeric parallel-stranded tetraplex with 3+1 5' g-tetrad interface, single-residue chain reversal loops and gag triad in the context of a(gggg) pentad
Reference
Phan AT, Kuryavyi VV, Ma J-B, Faure A, Andreola M-L, Patel DJ (2005): "An interlocked dimeric parallel-stranded DNA quadruplex: A potent inhibitor of HIV-1 integrase." Proc.Natl.Acad.Sci.USA, 102, 634-639. doi: 10.1073/pnas.0406278102.
Abstract
We report on the NMR-based solution structure of the 93del d(GGGGTGGGAGGAGGGT) aptamer, a potent nanomolar inhibitor of HIV-1 integrase. This guanine-rich DNA sequence adopts an unusually stable dimeric quadruplex architecture in K+ solution. Within each 16-nt monomer subunit, which contains one A.(G.G.G.G) pentad sandwiched between two G.G.G.G tetrads, all G-stretches are parallel, and all guanines are anti with the exception of G1, which is syn. Dimer formation is achieved through mutual pairing of G1 of one monomer, with G2, G6, and G13 of the other monomer, to complete G.G.G.G tetrad formation. There are three single-nucleotide double-chain-reversal loops within each monomer fold, such that the first (T5) and third (A12) loops bridge three G-tetrad layers, whereas the second (A9) loop bridges two G-tetrad layers and participates in A.(G.G.G.G) pentad formation. Results of NMR and of integrase inhibition assays on loop-modified sequences allowed us to propose a strategy toward the potential design of improved HIV-1 integrase inhibitors. Finally, we propose a model, based on molecular docking approaches, for positioning the 93del dimeric DNA quadruplex within a basic channel/canyon formed between subunits of a dimer of dimers of HIV-1 integrase.
G4 notes
6 G-tetrads, 1 G4 helix, 2 G4 stems, 1 G4 coaxial stack, 2(-P-P-P), parallel(4+0), UUUU, coaxial interfaces: 5'/5'-SEPARATED

Base-block schematics in six views

PyMOL session file PDB file View in 3Dmol.js

List of 6 G-tetrads

 1 glyco-bond=s--- sugar=---. groove=w--n planarity=0.091 type=planar nts=4 GGGG A.DG1,B.DG6,B.DG2,B.DG13
 2 glyco-bond=--s- sugar=---. groove=-wn- planarity=0.091 type=planar nts=4 GGGG A.DG2,A.DG6,B.DG1,A.DG13
 3 glyco-bond=---- sugar=---- groove=---- planarity=0.125 type=planar nts=4 GGGG A.DG3,A.DG7,A.DG10,A.DG14
 4 glyco-bond=---- sugar=---- groove=---- planarity=0.141 type=planar nts=4 GGGG A.DG4,A.DG8,A.DG11,A.DG15
 5 glyco-bond=---- sugar=---- groove=---- planarity=0.126 type=planar nts=4 GGGG B.DG3,B.DG7,B.DG10,B.DG14
 6 glyco-bond=---- sugar=---- groove=---- planarity=0.141 type=planar nts=4 GGGG B.DG4,B.DG8,B.DG11,B.DG15

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-tetrad layers, inter-molecular, with 2 stems

 1  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG4,A.DG8,A.DG11,A.DG15
 2  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG3,A.DG7,A.DG10,A.DG14
 3  glyco-bond=--s- sugar=---. groove=-wn- WC-->Major nts=4 GGGG A.DG2,A.DG6,B.DG1,A.DG13
 4  glyco-bond=s--- sugar=---. groove=w--n Major-->WC nts=4 GGGG A.DG1,B.DG6,B.DG2,B.DG13
 5  glyco-bond=---- sugar=---- groove=---- Major-->WC nts=4 GGGG B.DG10,B.DG7,B.DG3,B.DG14
 6  glyco-bond=---- sugar=---- groove=---- Major-->WC nts=4 GGGG B.DG11,B.DG8,B.DG4,B.DG15
  step#1  mp(<<,backward) area=10.47 rise=3.45 twist=30.8
  step#2  mp(<<,backward) area=9.56  rise=3.45 twist=34.1
  step#3  mm(<>,outward)  area=8.74  rise=3.35 twist=25.0
  step#4  pm(>>,forward)  area=9.56  rise=3.45 twist=34.1
  step#5  pm(>>,forward)  area=10.49 rise=3.45 twist=30.8
  strand#1 DNA glyco-bond=---s-- sugar=------ nts=6 GGGGGG A.DG4,A.DG3,A.DG2,A.DG1,B.DG10,B.DG11
  strand#2 DNA glyco-bond=------ sugar=------ nts=6 GGGGGG A.DG8,A.DG7,A.DG6,B.DG6,B.DG7,B.DG8
  strand#3 DNA glyco-bond=--s--- sugar=------ nts=6 GGGGGG A.DG11,A.DG10,B.DG1,B.DG2,B.DG3,B.DG4
  strand#4 DNA glyco-bond=------ sugar=--..-- nts=6 GGGGGG A.DG15,A.DG14,A.DG13,B.DG13,B.DG14,B.DG15

Download PDB file
Interactive view in 3Dmol.js
5 stacking diagrams 
 1  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG4,A.DG8,A.DG11,A.DG15
 2  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG3,A.DG7,A.DG10,A.DG14
  step#1  mp(<<,backward) area=10.47 rise=3.45 twist=30.8

Download PDB file
Interactive view in 3Dmol.js

 
 2  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG3,A.DG7,A.DG10,A.DG14
 3  glyco-bond=--s- sugar=---. groove=-wn- WC-->Major nts=4 GGGG A.DG2,A.DG6,B.DG1,A.DG13
  step#2  mp(<<,backward) area=9.56  rise=3.45 twist=34.1

Download PDB file
Interactive view in 3Dmol.js

 
 3  glyco-bond=--s- sugar=---. groove=-wn- WC-->Major nts=4 GGGG A.DG2,A.DG6,B.DG1,A.DG13
 4  glyco-bond=s--- sugar=---. groove=w--n Major-->WC nts=4 GGGG A.DG1,B.DG6,B.DG2,B.DG13
  step#3  mm(<>,outward)  area=8.74  rise=3.35 twist=25.0

Download PDB file
Interactive view in 3Dmol.js

 
 4  glyco-bond=s--- sugar=---. groove=w--n Major-->WC nts=4 GGGG A.DG1,B.DG6,B.DG2,B.DG13
 5  glyco-bond=---- sugar=---- groove=---- Major-->WC nts=4 GGGG B.DG10,B.DG7,B.DG3,B.DG14
  step#4  pm(>>,forward)  area=9.56  rise=3.45 twist=34.1

Download PDB file
Interactive view in 3Dmol.js

 
 5  glyco-bond=---- sugar=---- groove=---- Major-->WC nts=4 GGGG B.DG10,B.DG7,B.DG3,B.DG14
 6  glyco-bond=---- sugar=---- groove=---- Major-->WC nts=4 GGGG B.DG11,B.DG8,B.DG4,B.DG15
  step#5  pm(>>,forward)  area=10.49 rise=3.45 twist=30.8

Download PDB file
Interactive view in 3Dmol.js

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, 2 G-tetrad layers, 3 loops, INTRA-molecular, UUUU, parallel, 2(-P-P-P), parallel(4+0)

 1  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG3,A.DG7,A.DG10,A.DG14
 2  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG4,A.DG8,A.DG11,A.DG15
  step#1  pm(>>,forward)  area=10.47 rise=3.45 twist=30.8
  strand#1  U DNA glyco-bond=-- sugar=-- nts=2 GG A.DG3,A.DG4
  strand#2  U DNA glyco-bond=-- sugar=-- nts=2 GG A.DG7,A.DG8
  strand#3  U DNA glyco-bond=-- sugar=-- nts=2 GG A.DG10,A.DG11
  strand#4  U DNA glyco-bond=-- sugar=-- nts=2 GG A.DG14,A.DG15
  loop#1 type=propeller strands=[#1,#2] nts=2 TG A.DT5,A.DG6
  loop#2 type=propeller strands=[#2,#3] nts=1 A A.DA9
  loop#3 type=propeller strands=[#3,#4] nts=2 AG A.DA12,A.DG13

Download PDB file
Interactive view in 3Dmol.js

Stem#2, 2 G-tetrad layers, 3 loops, INTRA-molecular, UUUU, parallel, 2(-P-P-P), parallel(4+0)

 1  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG B.DG3,B.DG7,B.DG10,B.DG14
 2  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG B.DG4,B.DG8,B.DG11,B.DG15
  step#1  pm(>>,forward)  area=10.49 rise=3.45 twist=30.8
  strand#1  U DNA glyco-bond=-- sugar=-- nts=2 GG B.DG3,B.DG4
  strand#2  U DNA glyco-bond=-- sugar=-- nts=2 GG B.DG7,B.DG8
  strand#3  U DNA glyco-bond=-- sugar=-- nts=2 GG B.DG10,B.DG11
  strand#4  U DNA glyco-bond=-- sugar=-- nts=2 GG B.DG14,B.DG15
  loop#1 type=propeller strands=[#1,#2] nts=2 TG B.DT5,B.DG6
  loop#2 type=propeller strands=[#2,#3] nts=1 A B.DA9
  loop#3 type=propeller strands=[#3,#4] nts=2 AG B.DA12,B.DG13

Download PDB file
Interactive view in 3Dmol.js

List of 1 G4 coaxial stack

 1 G4 helix#1 contains 2 G4 stems: [#1,#2]  [5'/5'-SEPARATED]