389d: Difference between revisions

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CRYSTAL STRUCTURE OF B-DNA WITH INCORPORATED 2'-DEOXY-2'-FLUORO-ARABINO-FURANOSYL THYMINES: IMPLICATIONS OF CONFORMATIONAL PREORGANIZATION FOR DUPLEX STABILITY

OverviewOverview

The fundamental conformational states of right-handed double helical DNA, the A- and B-forms, are associated with distinct puckers of the sugar moieties. The furanose conformation itself is affected by the steric and electronic nature of the ring substituents. For example, a strongly electronegative substituent at the C2' position, such as in the 2'-deoxy-2'-fluoro ribo furanosyl analogue, will drive the conformational equilibrium towards the C3'- endo type (north). Conversely, the 2'-deoxy-2'-fluoro arabino furanosyl modification with opposite stereochemistry at C2' appears to have a preference for a C2'- endo type pucker (south). Incorporation of 2'-fluoroarabinofuranosyl thymines was previously shown to enhance the thermodynamic stability of B-DNA duplexes. We have determined the crystal structures of the B-DNA dodecamer duplexes [d(CGCGAASSCGCG)]2and [d(CGCGAASTCGCG)]2with incorporated 2'-deoxy-2'-fluoroarabinofuranosyl thymines S (south) at 1.55 A resolution. In the crystal structures, all S residues adopt an O4'- endo conformation (east), well compatible with an overall B-form duplex geometry. In addition to the increased rigidity of S nucleosides, a clathrate-like ordered water structure around the 2'-fluorines may account for the observed larger thermodynamic stability of DNA duplexes containing 2'-deoxy-2'-fluoroarabino thymidines.

About this StructureAbout this Structure

389D is a Protein complex structure of sequences from [1] with as ligand. Full crystallographic information is available from OCA.

ReferenceReference

Crystal structures of B-DNA with incorporated 2'-deoxy-2'-fluoro-arabino-furanosyl thymines: implications of conformational preorganization for duplex stability., Berger I, Tereshko V, Ikeda H, Marquez VE, Egli M, Nucleic Acids Res. 1998 May 15;26(10):2473-80. PMID:9580702

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 ==Overview==
-The fundamental conformational states of right-handed double helical DNA, the A- and B-forms, are associated with distinct puckers of the sugar, moieties. The furanose conformation itself is affected by the steric and, electronic nature of the ring substituents. For example, a strongly, electronegative substituent at the C2' position, such as in the, 2'-deoxy-2'-fluoro ribo furanosyl analogue, will drive the conformational, equilibrium towards the C3'- endo type (north). Conversely, the, 2'-deoxy-2'-fluoro arabino furanosyl modification with opposite, stereochemistry at C2' appears to have a preference for a C2'- endo type, pucker (south). Incorporation of 2'-fluoroarabinofuranosyl thymines was, previously shown to enhance the thermodynamic stability of B-DNA duplexes., We have determined the crystal structures of the B-DNA dodecamer duplexes, [d(CGCGAASSCGCG)]2and [d(CGCGAASTCGCG)]2with incorporated, 2'-deoxy-2'-fluoroarabinofuranosyl thymines S (south) at 1.55 A, resolution. In the crystal structures, all S residues adopt an O4'- endo, conformation (east), well compatible with an overall B-form duplex, geometry. In addition to the increased rigidity of S nucleosides, a, clathrate-like ordered water structure around the 2'-fluorines may account, for the observed larger thermodynamic stability of DNA duplexes containing, 2'-deoxy-2'-fluoroarabino thymidines.
+The fundamental conformational states of right-handed double helical DNA, the A- and B-forms, are associated with distinct puckers of the sugar moieties. The furanose conformation itself is affected by the steric and electronic nature of the ring substituents. For example, a strongly electronegative substituent at the C2' position, such as in the 2'-deoxy-2'-fluoro ribo furanosyl analogue, will drive the conformational equilibrium towards the C3'- endo type (north). Conversely, the 2'-deoxy-2'-fluoro arabino furanosyl modification with opposite stereochemistry at C2' appears to have a preference for a C2'- endo type pucker (south). Incorporation of 2'-fluoroarabinofuranosyl thymines was previously shown to enhance the thermodynamic stability of B-DNA duplexes. We have determined the crystal structures of the B-DNA dodecamer duplexes [d(CGCGAASSCGCG)]2and [d(CGCGAASTCGCG)]2with incorporated 2'-deoxy-2'-fluoroarabinofuranosyl thymines S (south) at 1.55 A resolution. In the crystal structures, all S residues adopt an O4'- endo conformation (east), well compatible with an overall B-form duplex geometry. In addition to the increased rigidity of S nucleosides, a clathrate-like ordered water structure around the 2'-fluorines may account for the observed larger thermodynamic stability of DNA duplexes containing 2'-deoxy-2'-fluoroarabino thymidines.
 ==About this Structure==
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 [[Category: Egli, M.]]
 [[Category: Ikeda, H.]]
-[[Category: Marquez, V.E.]]
+[[Category: Marquez, V E.]]
 [[Category: Tereshko, V.]]
 [[Category: MG]]
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 [[Category: modified]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jan 29 21:37:41 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:02:32 2008''