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PDBsum entry 2qef

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dna_rna links
DNA PDB id
2qef
Jmol
Contents
DNA/RNA
Waters ×96
PDB id:
2qef
Name: DNA
Title: X-ray structure of 7-deaza-dg and z3du modified duplex cgcgaatxczcg
Structure: DNA (5'-d( Dcp Dgp Dcp Dgp Dap Dap Dtp (Zdu) p Dcp (7Gu)p Dcp Dg)-3'). Chain: a, b. Engineered: yes. Other_details: ddd2+/z10
Source: Synthetic: yes. Other_details: the oligodeoxynucleotide 5'-d(cgcgaatxczcg)- 3' (ddd2+/z10) was synthesized and purified using reversed- phase semipreparative hplc (phenomenex, phenyl-hexyl, 5 m, 250 10.0 mm) equilibrated with 0.1 m ammonium formate (ph 7.0) and desalted using g25 column.
Resolution:
1.60Å     R-factor:   0.181     R-free:   0.231
Authors: F.Wang,F.Li,M.Ganguly,L.A.Marky,B.Gold,M.Egli,M.P.Stone
Key ref: F.Wang et al. (2008). A bridging water anchors the tethered 5-(3-aminopropyl)-2'-deoxyuridine amine in the DNA major groove proximate to the N+2 C.G base pair: implications for formation of interstrand 5'-GNC-3' cross-links by nitrogen mustards. Biochemistry, 47, 7147-7157. PubMed id: 18549246
Date:
25-Jun-07     Release date:   06-May-08    
 Headers
 References

 

 
Biochemistry 47:7147-7157 (2008)
PubMed id: 18549246  
 
 
A bridging water anchors the tethered 5-(3-aminopropyl)-2'-deoxyuridine amine in the DNA major groove proximate to the N+2 C.G base pair: implications for formation of interstrand 5'-GNC-3' cross-links by nitrogen mustards.
F.Wang, F.Li, M.Ganguly, L.A.Marky, B.Gold, M.Egli, M.P.Stone.
 
  ABSTRACT  
 
Site-specific insertion of 5-(3-aminopropyl)-2'-deoxyuridine (Z3dU) and 7-deaza-dG into the Dickerson-Drew dodecamers 5'-d(C (1)G (2)C (3)G (4)A (5)A (6)T (7)T (8)C (9) Z (10)C (11)G (12))-3'.5'-d(C (13)G (14)C (15)G (16)A (17)A (18)T (19)T (20)C (21) Z (22)C (23)G (24))-3' (named DDD (Z10)) and 5'-d(C (1)G (2)C (3)G (4)A (5)A (6)T (7) X (8)C (9) Z (10)C (11)G (12))-3'.5'-d(C (13)G (14)C (15)G (16)A (17)A (18)T (19) X (20)C (21) Z (22)C (23)G (24))-3' (named DDD (2+Z10)) (X = Z3dU; Z = 7-deaza-dG) suggests a mechanism underlying the formation of interstrand N+2 DNA cross-links by nitrogen mustards, e.g., melphalan and mechlorethamine. Analysis of the DDD (2+Z10) duplex reveals that the tethered cations at base pairs A (5).X (20) and X (8).A (17) extend within the major groove in the 3'-direction, toward conserved Mg (2+) binding sites located adjacent to N+2 base pairs C (3).Z (22) and Z (10).C (15). Bridging waters located between the tethered amines and either Z (10) or Z (22) O (6) stabilize the tethered cations and allow interactions with the N + 2 base pairs without DNA bending. Incorporation of 7-deaza-dG into the DDD (2+Z10) duplex weakens but does not eliminate electrostatic interactions between tethered amines and Z (10) O (6) and Z (22) O (6). The results suggest a mechanism by which tethered N7-dG aziridinium ions, the active species involved in formation of interstrand 5'-GNC-3' cross-links by nitrogen mustards, modify the electrostatics of the major groove and position the aziridinium ions proximate to the major groove edge of the N+2 C.G base pair, facilitating interstrand cross-linking.