Summary information and primary citation

PDB-id
2a5r
Class
DNA
Method
NMR
Summary
Complex of tetra-(4-n-methylpyridyl) porphin with monomeric parallel-stranded DNA tetraplex, snap-back 3+1 3' g-tetrad, single-residue chain reversal loops, gag triad in the context of gaag diagonal loop, c-myc promoter, NMR, 6 struct.
Reference
Phan AT, Kuryavyi V, Gaw HY, Patel DJ (2005): "Small-molecule interaction with a five-guanine-tract G-quadruplex structure from the human MYC promoter." Nat.Chem.Biol., 1, 167-173. doi: 10.1038/nchembio723.
Abstract
It has been widely accepted that DNA can adopt other biologically relevant structures beside the Watson-Crick double helix. One recent important example is the guanine-quadruplex (G-quadruplex) structure formed by guanine tracts found in the MYC (or c-myc) promoter region, which regulates the transcription of the MYC oncogene. Stabilization of this G-quadruplex by ligands, such as the cationic porphyrin TMPyP4, decreases the transcriptional level of MYC. Here, we report the first structure of a DNA fragment containing five guanine tracts from this region. An unusual G-quadruplex fold, which was derived from NMR restraints using unambiguous model-independent resonance assignment approaches, involves a core of three stacked guanine tetrads formed by four parallel guanine tracts with all anti guanines and a snapback 3'-end syn guanine. We have determined the structure of the complex formed between this G-quadruplex and TMPyP4. This structural information, combined with details of small-molecule interaction, provides a platform for the design of anticancer drugs targeting multi-guanine-tract sequences that are found in the MYC and other oncogenic promoters, as well as in telomeres.
G4 notes
3 G-tetrads, 1 G4 helix, 1 G4 stem, UUUU, parallel, 4+0, 2(-P-P-P)

Cartoon-block schematics in six views (download the tarball)

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List of 3 G-tetrads

 1 glyco-bond=---- sugar=---- groove=---- planarity=0.114 type=planar O+ nts=4 GGGG A.DG4,A.DG8,A.DG13,A.DG17
 2 glyco-bond=---- sugar=.--- groove=---- planarity=0.240 type=other  O+ nts=4 GGGG A.DG5,A.DG9,A.DG14,A.DG18
 3 glyco-bond=-s-- sugar=---- groove=wn-- planarity=0.304 type=other  Z- nts=4 GGGG A.DG6,A.DG24,A.DG15,A.DG19

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.DG4,A.DG8,A.DG13,A.DG17
 2  glyco-bond=---- sugar=.--- groove=---- WC-->Major O+ nts=4 GGGG A.DG5,A.DG9,A.DG14,A.DG18
 3  glyco-bond=-s-- sugar=---- groove=wn-- WC-->Major Z- nts=4 GGGG A.DG6,A.DG24,A.DG15,A.DG19
  step#1  pm(>>,forward)  area=14.02 rise=3.22 twist=27.8
  step#2  pm(>>,forward)  area=11.66 rise=3.28 twist=31.7
  strand#1 DNA glyco-bond=--- sugar=-.- nts=3 GGG A.DG4,A.DG5,A.DG6
  strand#2 DNA glyco-bond=--s sugar=--- nts=3 GGG A.DG8,A.DG9,A.DG24
  strand#3 DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG13,A.DG14,A.DG15
  strand#4 DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG17,A.DG18,A.DG19

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2 stacking diagrams 
 1  glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG4,A.DG8,A.DG13,A.DG17
 2  glyco-bond=---- sugar=.--- groove=---- WC-->Major O+ nts=4 GGGG A.DG5,A.DG9,A.DG14,A.DG18
  step#1  pm(>>,forward)  area=14.02 rise=3.22 twist=27.8

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 2  glyco-bond=---- sugar=.--- groove=---- WC-->Major O+ nts=4 GGGG A.DG5,A.DG9,A.DG14,A.DG18
 3  glyco-bond=-s-- sugar=---- groove=wn-- WC-->Major Z- nts=4 GGGG A.DG6,A.DG24,A.DG15,A.DG19
  step#2  pm(>>,forward)  area=11.66 rise=3.28 twist=31.7

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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, 2 G-tetrads, 3 loops, INTRA-molecular, UUUU, parallel, 4+0, 2(-P-P-P)
 1  glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG A.DG4,A.DG8,A.DG13,A.DG17
 2  glyco-bond=---- sugar=.--- groove=---- WC-->Major O+ nts=4 GGGG A.DG5,A.DG9,A.DG14,A.DG18
  step#1  pm(>>,forward)  area=14.02 rise=3.22 twist=27.8
  strand#1  U DNA glyco-bond=-- sugar=-. nts=2 GG A.DG4,A.DG5
  strand#2  U DNA glyco-bond=-- sugar=-- nts=2 GG A.DG8,A.DG9
  strand#3  U DNA glyco-bond=-- sugar=-- nts=2 GG A.DG13,A.DG14
  strand#4  U DNA glyco-bond=-- sugar=-- nts=2 GG A.DG17,A.DG18
  loop#1 type=propeller strands=[#1,#2] nts=2 GT A.DG6,A.DT7
  loop#2 type=propeller strands=[#2,#3] nts=3 gGA A.DI10,A.DG11,A.DA12
  loop#3 type=propeller strands=[#3,#4] nts=2 GT A.DG15,A.DT16

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List of 1 non-stem G4-loop (including the two closing Gs)

 1 type=diagonal  helix=#1 nts=6 GGAAGG A.DG19,A.DG20,A.DA21,A.DA22,A.DG23,A.DG24