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PDBsum entry 1s32
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protein dna_rna ligands metals Protein-protein interface(s) links
Structural protein/DNA PDB id
1s32

 

 

 

 

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JSmol PyMol  
Contents
Protein chains
98 a.a. *
81 a.a. *
107 a.a. *
101 a.a. *
88 a.a. *
DNA/RNA
Ligands
IMT-PYB-IMT-PYB-
ABU-PYB-PYB-PYB-
PYB-BAL-DIB ×2
OGG
Metals
_CL ×4
_MN ×14
Waters ×888
* Residue conservation analysis
PDB id:
1s32
Name: Structural protein/DNA
Title: Molecular recognition of the nucleosomal 'supergroove'
Structure: Palindromic alpha-satellite 146 bp DNA fragment. Chain: i, j. Engineered: yes. Histone h3. Chain: a, e. Engineered: yes. Histone h4. Chain: b, f. Engineered: yes.
Source: Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Xenopus laevis. African clawed frog. Organism_taxid: 8355. Gene: loc121398065. Expressed in: escherichia coli.
Biol. unit: Undecamer (from PQS)
Resolution:
2.05Å     R-factor:   0.219     R-free:   0.243
Authors: R.S.Edayathumangalam,P.Weyermann,J.M.Gottesfeld,P.B.Dervan,K.Luger
Key ref:
R.S.Edayathumangalam et al. (2004). Molecular recognition of the nucleosomal "supergroove". Proc Natl Acad Sci U S A, 101, 6864-6869. PubMed id: 15100411 DOI: 10.1073/pnas.0401743101
Date:
12-Jan-04     Release date:   11-May-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P84233  (H32_XENLA) -  Histone H3.2 from Xenopus laevis
Seq:
Struc: 		136 a.a.
98 a.a.*
Protein chain
Pfam   ArchSchema ?
P62799  (H4_XENLA) -  Histone H4 from Xenopus laevis
Seq:
Struc: 		103 a.a.
81 a.a.
Protein chains
Pfam   ArchSchema ?
P06897  (H2A1_XENLA) -  Histone H2A type 1 from Xenopus laevis
Seq:
Struc: 		130 a.a.
107 a.a.*
Protein chains
Pfam   ArchSchema ?
P02281  (H2B11_XENLA) -  Histone H2B 1.1 from Xenopus laevis
Seq:
Struc: 		126 a.a.
101 a.a.*
Protein chain
Pfam   ArchSchema ?
P62799  (H4_XENLA) -  Histone H4 from Xenopus laevis
Seq:
Struc: 		103 a.a.
88 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

DNA/RNA chains
  A-T-C-A-A-T-A-T-C-C-A-C-C-T-G-C-A-G-A-T-T-C-T-A-C-C-A-A-A-A-G-T-G-T-A-T-T-T-G- 146 bases
  A-T-C-A-A-T-A-T-C-C-A-C-C-T-G-C-A-G-A-T-T-C-T-A-C-C-A-A-A-A-G-T-G-T-A-T-T-T-G- 146 bases

 

 
DOI no: 10.1073/pnas.0401743101 Proc Natl Acad Sci U S A 101:6864-6869 (2004)
PubMed id: 15100411  
 
 
Molecular recognition of the nucleosomal "supergroove".
R.S.Edayathumangalam, P.Weyermann, J.M.Gottesfeld, P.B.Dervan, K.Luger.
 
  ABSTRACT  
 
Chromatin is the physiological substrate in all processes involving eukaryotic DNA. By organizing 147 base pairs of DNA into two tight superhelical coils, the nucleosome generates an architecture where DNA regions that are 80 base pairs apart on linear DNA are brought into close proximity, resulting in the formation of DNA "supergrooves." Here, we report the design of a hairpin polyamide dimer that targets one such supergroove. The 2-A crystal structure of the nucleosome-polyamide complex shows that the bivalent "clamp" effectively crosslinks the two gyres of the DNA superhelix, improves positioning of the DNA on the histone octamer, and stabilizes the nucleosome against dissociation. Our findings identify nucleosomal supergrooves as platforms for molecular recognition of condensed eukaryotic DNA. In vivo, supergrooves may foster synergistic protein-protein interactions by bringing two regulatory elements into juxtaposition. Because supergroove formation is independent of the translational position of the DNA on the histone octamer, accurate nucleosome positioning over regulatory elements is not required for supergroove participation in eukaryotic gene regulation.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Site-specific recognition of nucleosomal DNA by clamp PAs. (A) NCP146 structure (PDB ID code 1AOI [PDB] , ref. 2) viewed with the superhelical axis along the z axis. The particle pseudo-two-fold dyad axis ( ) is shown for orientation. DNA (blue and white) and associated histone proteins (H2A, yellow; H2B, red; H3, blue; H4, green) are shown in sphere or surface representation. (B) Supergrooves in NCP146. Shown is a different view of NCP146 with the superhelical axis along the y axis. Color scheme is the same as in A. One of the DNA supergrooves is indicated by two asterisks. (C) Chemical structures of clamp PAs, PW12 to -14. (D) Hydrogen bonding model of PW12 to its target DNA site. Circles with dots represent lone pairs of N3 of purines and O2 of pyrimidines. Circles containing H represent the N2 hydrogen of guanine. Putative hydrogen bonds are illustrated by dotted lines. 		Figure 3.
Fig. 3. Schematic illustration of the predicted effect of PA clamps on nucleosome dissociation. In the absence of ligand binding, nucleosome dissociation initiates with unraveling of the DNA ends, followed by dissociation of the (H2A-H2B) dimers, and finally by the dissociation of the (H3-H4)[2] tetramer. Binding clamp to the nucleosomes leads to the formation of a closed 80-bp DNA supercoil that prevents further disassembly of the nucleosomes.
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21208404 A.Marathe, and M.Bansal (2011).
An ensemble of B-DNA dinucleotide geometries lead to characteristic nucleosomal DNA structure and provide plasticity required for gene expression.
  BMC Struct Biol, 11, 1.  
21176878 S.Tan, and C.A.Davey (2011).
Nucleosome structural studies.
  Curr Opin Struct Biol, 21, 128-136.  
21073701 C.Nikolaou, S.Althammer, M.Beato, and R.Guigó (2010).
Structural constraints revealed in consistent nucleosome positions in the genome of S. cerevisiae.
  Epigenetics Chromatin, 3, 20.  
20026584 G.E.Davey, B.Wu, Y.Dong, U.Surana, and C.A.Davey (2010).
DNA stretching in the nucleosome facilitates alkylation by an intercalating antitumour agent.
  Nucleic Acids Res, 38, 2081-2088.
PDB code: 3kuy
20628623 S.M.Reynolds, J.A.Bilmes, and W.S.Noble (2010).
Learning a weighted sequence model of the nucleosome core and linker yields more accurate predictions in Saccharomyces cerevisiae and Homo sapiens.
  PLoS Comput Biol, 6, e1000834.  
19666554 D.M.Chenoweth, and P.B.Dervan (2009).
Allosteric modulation of DNA by small molecules.
  Proc Natl Acad Sci U S A, 106, 13175-13179.
PDB codes: 3i5e 3i5l
  20046924 R.C.Todd, and S.J.Lippard (2009).
Inhibition of transcription by platinum antitumor compounds.
  Metallomics, 1, 280-291.  
18753620 D.A.Harki, N.Satyamurthy, D.B.Stout, M.E.Phelps, and P.B.Dervan (2008).
In vivo imaging of pyrrole-imidazole polyamides with positron emission tomography.
  Proc Natl Acad Sci U S A, 105, 13039-13044.  
18477633 D.Svozil, J.Kalina, M.Omelka, and B.Schneider (2008).
DNA conformations and their sequence preferences.
  Nucleic Acids Res, 36, 3690-3706.  
18924284 G.E.Davey, and C.A.Davey (2008).
Chromatin - a new, old drug target?
  Chem Biol Drug Des, 72, 165-170.  
18692405 K.A.Schug, M.D.Joshi, P.Frycák, N.M.Maier, and W.Lindner (2008).
Investigation of monovalent and bivalent enantioselective molecular recognition by electrospray ionization-mass spectrometry and tandem mass spectrometry.
  J Am Soc Mass Spectrom, 19, 1629-1642.  
18773096 R.Sathyapriya, M.S.Vijayabaskar, and S.Vishveshwara (2008).
Insights into protein-DNA interactions through structure network analysis.
  PLoS Comput Biol, 4, e1000170.  
18424496 T.C.Bishop (2008).
Geometry of the nucleosomal DNA superhelix.
  Biophys J, 95, 1007-1017.  
17264930 M.J.Hannon (2007).
Supramolecular DNA recognition.
  Chem Soc Rev, 36, 280-295.  
16478715 G.S.Couch, D.K.Hendrix, and T.E.Ferrin (2006).
Nucleic acid visualization with UCSF Chimera.
  Nucleic Acids Res, 34, e29.  
15703305 K.L.Buchmueller, A.M.Staples, P.B.Uthe, C.M.Howard, K.A.Pacheco, K.K.Cox, J.A.Henry, S.L.Bailey, S.M.Horick, B.Nguyen, W.D.Wilson, and M.Lee (2005).
Molecular recognition of DNA base pairs by the formamido/pyrrole and formamido/imidazole pairings in stacked polyamides.
  Nucleic Acids Res, 33, 912-921.  
15556999 B.Z.Olenyuk, G.J.Zhang, J.M.Klco, N.G.Nickols, W.G.Kaelin, and P.B.Dervan (2004).
Inhibition of vascular endothelial growth factor with a sequence-specific hypoxia response element antagonist.
  Proc Natl Acad Sci U S A, 101, 16768-16773.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

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