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PDBsum entry 101d

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dna_rna ligands metals links
DNA PDB id
101d
Jmol
Contents
DNA/RNA
Ligands
_NT
Metals
_MG
Waters ×36
PDB id:
101d
Name: DNA
Title: Refinement of netropsin bound to dna: bias and feedback in electron density map interpretation
Structure: DNA (5'-d( Cp Gp Cp Gp Ap Ap Tp Tp (Cbr) p Gp Cp G)-3'). Chain: a, b. Engineered: yes
Source: Synthetic: yes
Biol. unit: Dimer (from PQS)
Resolution:
2.25Å     R-factor:   0.163     R-free:   0.252
Authors: D.S.Goodsell,M.L.Kopka,R.E.Dickerson
Key ref:
D.S.Goodsell et al. (1995). Refinement of netropsin bound to DNA: bias and feedback in electron density map interpretation. Biochemistry, 34, 4983-4993. PubMed id: 7711020 DOI: 10.1021/bi00015a009
Date:
14-Dec-94     Release date:   27-Feb-95    
 Headers
 References

 

 
DOI no: 10.1021/bi00015a009 Biochemistry 34:4983-4993 (1995)
PubMed id: 7711020  
 
 
Refinement of netropsin bound to DNA: bias and feedback in electron density map interpretation.
D.S.Goodsell, M.L.Kopka, R.E.Dickerson.
 
  ABSTRACT  
 
The X-ray crystal structure of the complex of the B-DNA dodecamer CGCGAATTCGCG with the antitumor drug netropsin has been reexamined to locate the drug accurately for computer-based drug design. The optimum solution is with the drug centered in the AATT region of the minor groove, making three good bifurcated hydrogen bonds with adenine N3 and thymine O2 atoms along the floor of the groove. Pyrrole rings of netropsin are packed against the C2 positions of adenines, leaving no room for the amine group of guanine and, hence, providing a structural rationale for the A.T specificity of netropsin. An alternative positioning in which the drug is shifted along the minor groove by ca. one-half base pair step is rejected on the basis of free R factor calculations and the appearance of the original drug-free difference maps. Final omit maps, although of more pleasing appearance, are not a dependable means of discriminating between right and wrong structures. The shifted alternative drug position ignores potential hydrogen bonding along the floor of the groove, provides no explanation for netropsin's observed A.T specificity, and is contradicted by NMR results [Patel, D. J. (1982) Proc. Natl. Acad. Sci. U.S.A. 79, 6424].
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21335028 C.A.Andac, A.M.Miandji, U.Hornemann, and N.Noyanalpan (2011).
Use of the parmbsc0 force field and trajectory analysis to study the binding of netropsin to the DNA fragment (5'CCAATTGG)(2) in the presence of excess NaCl salt in aqueous solution.
  Int J Biol Macromol, 48, 531-539.  
19906722 G.Zheng, A.V.Colasanti, X.J.Lu, and W.K.Olson (2010).
3DNALandscapes: a database for exploring the conformational features of DNA.
  Nucleic Acids Res, 38, D267-D274.  
20633350 I.P.Gerothanassis (2010).
Oxygen-17 NMR spectroscopy: basic principles and applications (part I).
  Prog Nucl Magn Reson Spectrosc, 56, 95.  
18798655 B.Nguyen, S.Neidle, and W.D.Wilson (2009).
A role for water molecules in DNA-ligand minor groove recognition.
  Acc Chem Res, 42, 11-21.  
18937643 M.A.Grant, R.M.Baron, A.A.Macias, M.D.Layne, M.A.Perrella, and A.C.Rigby (2009).
Netropsin improves survival from endotoxaemia by disrupting HMGA1 binding to the NOS2 promoter.
  Biochem J, 418, 103-112.  
19154116 Q.Dong, E.Stellwagen, and N.C.Stellwagen (2009).
Monovalent cation binding in the minor groove of DNA A-tracts.
  Biochemistry, 48, 1047-1055.  
17623435 Z.Shen, X.Liu, X.Zhou, A.Liang, D.Wu, L.Yu, Z.Dai, J.Qin, and B.Lin (2007).
Quantitative evaluation of the interaction between netropsin and double stranded oligodeoxynucleotides by microfabricated capillary array electrophoresis.
  J Sep Sci, 30, 1544-1548.  
16731550 J.Dolenc, R.Baron, C.Oostenbrink, J.Koller, and W.F.van Gunsteren (2006).
Configurational entropy change of netropsin and distamycin upon DNA minor-groove binding.
  Biophys J, 91, 1460-1470.  
15687382 J.Dolenc, C.Oostenbrink, J.Koller, and W.F.van Gunsteren (2005).
Molecular dynamics simulations and free energy calculations of netropsin and distamycin binding to an AAAAA DNA binding site.
  Nucleic Acids Res, 33, 725-733.  
16049022 K.D.Goodwin, E.C.Long, and M.M.Georgiadis (2005).
A host-guest approach for determining drug-DNA interactions: an example using netropsin.
  Nucleic Acids Res, 33, 4106-4116.
PDB codes: 1ztt 1ztw
16008554 K.Van Hecke, P.C.Nam, M.T.Nguyen, and L.Van Meervelt (2005).
Netropsin interactions in the minor groove of d(GGCCAATTGG) studied by a combination of resolution enhancement and ab initio calculations.
  FEBS J, 272, 3531-3541.
PDB code: 1z8v
15918722 R.D.Parra, S.Bulusu, and X.C.Zeng (2005).
Cooperative effects in two-dimensional ring-like networks of three-center hydrogen bonding interactions.
  J Chem Phys, 122, 184325.  
12071949 K.Uytterhoeven, J.Sponer, and L.Van Meervelt (2002).
Two 1 : 1 binding modes for distamycin in the minor groove of d(GGCCAATTGG).
  Eur J Biochem, 269, 2868-2877.
PDB codes: 1jtl 1k2z
12115142 B.Wellenzohn, W.Flader, R.H.Winger, A.Hallbrucker, E.Mayer, and K.R.Liedl (2001).
Influence of netropsin's charges on the minor groove width of d(CGCGAATTCGCG)2.
  Biopolymers, 61, 276-286.  
11509372 B.Wellenzohn, W.Flader, R.H.Winger, A.Hallbrucker, E.Mayer, and K.R.Liedl (2001).
Significance of ligand tails for interaction with the minor groove of B-DNA.
  Biophys J, 81, 1588-1599.  
11695668 R.D.Parra, H.Zeng, J.Zhu, C.Zheng, X.C.Zeng, and B.Gong (2001).
Stable three-center hydrogen bonding in a partially rigidified structure.
  Chemistry, 7, 4352-4357.  
10639130 V.P.Denisov, and B.Halle (2000).
Sequence-specific binding of counterions to B-DNA.
  Proc Natl Acad Sci U S A, 97, 629-633.  
10580832 B.S.Reddy, S.M.Sondhi, and J.W.Lown (1999).
Synthetic DNA minor groove-binding drugs.
  Pharmacol Ther, 84, 1.  
10600105 D.Vlieghe, J.Sponer, and L.Van Meervelt (1999).
Crystal structure of d(GGCCAATTGG) complexed with DAPI reveals novel binding mode.
  Biochemistry, 38, 16443-16451.
PDB code: 432d
10089411 F.van den Akker, and W.G.Hol (1999).
Difference density quality (DDQ): a method to assess the global and local correctness of macromolecular crystal structures.
  Acta Crystallogr D Biol Crystallogr, 55, 206-218.  
10373586 J.Aymami, C.M.Nunn, and S.Neidle (1999).
DNA minor groove recognition of a non-self-complementary AT-rich sequence by a tris-benzimidazole ligand.
  Nucleic Acids Res, 27, 2691-2698.
PDB codes: 458d 459d
9493396 S.Neidle, and C.M.Nunn (1998).
Crystal structures of nucleic acids and their drug complexes.
  Nat Prod Rep, 15, 1.  
9622486 X.Shui, L.McFail-Isom, G.G.Hu, and L.D.Williams (1998).
The B-DNA dodecamer at high resolution reveals a spine of water on sodium.
  Biochemistry, 37, 8341-8355.
PDB code: 355d
9125500 C.M.Nunn, E.Garman, and S.Neidle (1997).
Crystal structure of the DNA decamer d(CGCAATTGCG) complexed with the minor groove binding drug netropsin.
  Biochemistry, 36, 4792-4799.
PDB code: 261d
9253416 J.R.Huth, C.A.Bewley, M.S.Nissen, J.N.Evans, R.Reeves, A.M.Gronenborn, and G.M.Clore (1997).
The solution structure of an HMG-I(Y)-DNA complex defines a new architectural minor groove binding motif.
  Nat Struct Biol, 4, 657-665.
PDB codes: 2ezd 2eze 2ezf 2ezg
9309219 M.L.Kopka, D.S.Goodsell, G.W.Han, T.K.Chiu, J.W.Lown, and R.E.Dickerson (1997).
Defining GC-specificity in the minor groove: side-by-side binding of the di-imidazole lexitropsin to C-A-T-G-G-C-C-A-T-G.
  Structure, 5, 1033-1046.
PDB code: 334d
9284321 Z.Song, O.N.Antzutkin, Y.K.Lee, S.C.Shekar, A.Rupprecht, and M.H.Levitt (1997).
Conformational transitions of the phosphodiester backbone in native DNA: two-dimensional magic-angle-spinning 31P-NMR of DNA fibers.
  Biophys J, 73, 1539-1552.  
  8843321 A.S.Levina, V.G.Metelev, A.S.Cohen, and P.C.Zamecnik (1996).
Conjugates of minor groove DNA binders with oligodeoxynucleotides: synthesis and properties.
  Antisense Nucleic Acid Drug Dev, 6, 75-85.  
8639524 C.A.Laughton, F.Tanious, C.M.Nunn, D.W.Boykin, W.D.Wilson, and S.Neidle (1996).
A crystallographic and spectroscopic study of the complex between d(CGCGAATTCGCG)2 and 2,5-bis(4-guanylphenyl)furan, an analogue of berenil. Structural origins of enhanced DNA-binding affinity.
  Biochemistry, 35, 5655-5661.
PDB code: 227d
8942984 C.Bailly, D.Payet, A.A.Travers, and M.J.Waring (1996).
PCR-based development of DNA substrates containing modified bases: an efficient system for investigating the role of the exocyclic groups in chemical and structural recognition by minor groove binding drugs and proteins.
  Proc Natl Acad Sci U S A, 93, 13623-13628.  
8614632 J.M.Rydzewski, W.Leupin, and W.Chazin (1996).
The width of the minor groove affects the binding of the bisquaternary heterocycle SN-6999 to duplex DNA.
  Nucleic Acids Res, 24, 1287-1293.  
8811103 L.Tabernero, J.Bella, and C.Alemán (1996).
Hydrogen bond geometry in DNA-minor groove binding drug complexes.
  Nucleic Acids Res, 24, 3458-3466.  
8877812 W.D.Wilson, L.Ratmeyer, M.Zhao, D.Ding, A.W.McConnaughie, A.Kumar, and D.W.Boykin (1996).
Design and analysis of RNA structure-specific agents as potential antivirals.
  J Mol Recognit, 9, 187-196.  
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 codes are shown on the right.