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1ac9

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Revision as of 09:18, 9 August 2017

SOLUTION STRUCTURE OF A DNA DECAMER CONTAINING THE ANTIVIRAL DRUG GANCICLOVIR: COMBINED USE OF NMR, RESTRAINED MOLECULAR DYNAMICS, AND FULL RELAXATION REFINEMENT, 6 STRUCTURES

Structural highlights

1ac9 is a 2 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

The nucleoside analog 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (ganciclovir, DHPG) is an antiviral drug that is used in the treatment of a variety of herpes viruses in immunocompromised patients and in a gene therapy protocol that has shown promising activity for the treatment of cancer. To probe the structural effects of ganciclovir when incorporated into DNA, we determined and compared the solution structure of a modified ganciclovir-containing decamer duplex [d(CTG)(ganciclovir)d(ATCCAG)]2 and a control duplex d[(CTGGATCCAG)]2 using nuclear magnetic resonance techniques. 1H and 31P resonances in both duplexes were assigned using a combination of 2-D 1H and 31P NMR experiments. Proton-proton distances determined from NOESY data and dihedral angles determined from DQF-COSY data were used in restrained molecular dynamics simulations starting from canonical A- and B-form DNA models. Both the control and ganciclovir sets of simulations converged to B-type structures. These structures were subjected to full relaxation matrix refinement to produce final structures that were in excellent agreement with the observed NOE intensities. Examination of the final ganciclovir-containing structures reveals that the base of the ganciclovir residue is hydrogen bonded to its complementary dC and is stacked in the helix; in fact, the base of ganciclovir exhibits increased stacking with the 5' base relative to the control. Interestingly, some of the most significant distortions in the structures occur 3' to the lesion site, including a noticeable kink in the sugar-phosphate backbone at this position. Further examination reveals that the backbone conformation, sugar pucker, and glycosidic torsion angle of the residue 3' to the lesion site all indicate an A-type conformation at this position. A possible correlation of these structural findings with results obtained from earlier biochemical studies will be discussed.

Solution structure of a DNA decamer containing the antiviral drug ganciclovir: combined use of NMR, restrained molecular dynamics, and full relaxation matrix refinement.,Foti M, Marshalko S, Schurter E, Kumar S, Beardsley GP, Schweitzer BI Biochemistry. 1997 May 6;36(18):5336-45. PMID:9154915^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Foti M, Marshalko S, Schurter E, Kumar S, Beardsley GP, Schweitzer BI. Solution structure of a DNA decamer containing the antiviral drug ganciclovir: combined use of NMR, restrained molecular dynamics, and full relaxation matrix refinement. Biochemistry. 1997 May 6;36(18):5336-45. PMID:9154915 doi:10.1021/bi962604e

1 Structural highlights
2 Publication Abstract from PubMed
3 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1ac9"

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 ==SOLUTION STRUCTURE OF A DNA DECAMER CONTAINING THE ANTIVIRAL DRUG GANCICLOVIR: COMBINED USE OF NMR, RESTRAINED MOLECULAR DYNAMICS, AND FULL RELAXATION REFINEMENT, 6 STRUCTURES==
 <StructureSection load='1ac9' size='340' side='right' caption='[[1ac9]], [[NMR_Ensembles_of_Models | 6 NMR models]]' scene=''>
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 <table><tr><td colspan='2'>[[1ac9]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AC9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1AC9 FirstGlance]. <br>
 </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=LGP:N9-1-HYDROXY-PROP-2-OXYMETHYL-GUANINE-3-MONOPHOSPHATE'>LGP</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ac9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ac9 OCA], [http://pdbe.org/1ac9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ac9 RCSB], [http://www.ebi.ac.uk/pdbsum/1ac9 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ac9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ac9 OCA], [http://pdbe.org/1ac9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ac9 RCSB], [http://www.ebi.ac.uk/pdbsum/1ac9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1ac9 ProSAT]</span></td></tr>
 </table>
 <div style="background-color:#fffaf0;">

1ac9

From Proteopedia

Revision as of 09:18, 9 August 2017

SOLUTION STRUCTURE OF A DNA DECAMER CONTAINING THE ANTIVIRAL DRUG GANCICLOVIR: COMBINED USE OF NMR, RESTRAINED MOLECULAR DYNAMICS, AND FULL RELAXATION REFINEMENT, 6 STRUCTURES

Structural highlights

Publication Abstract from PubMed

References

Contents

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