1d45: Difference between revisions

Revision as of 13:12, 21 February 2008

DNA DODECAMER C-G-C-G-A-A-T-T-C-G-C-G/HOECHST 33258 COMPLEX:-25 DEGREES C, PIPERAZINE DOWN

OverviewOverview

The crystal structure of the complex of Hoechst 33258 and the DNA dodecamer C-G-C-G-A-A-T-T-C-G-C-G has been solved from X-ray data collected at three different low temperatures (0, -25, and -100 degrees C). Such temperatures have permitted collection of higher resolution data (2.0, 1.9, and 2.0 A, respectively) than with previous X-ray studies of the same complex. In all three cases, the drug is located in the narrow central A-A-T-T region of the minor groove. Data analyses at -25 and -100 degrees C (each with a 1:1 drug/DNA ratio in the crystallizing solution) suggest a unique orientation for the drug. In contrast, two orientations of the drug were found equally possible at 0 degrees C with a 2:1 drug/DNA ratio in solution. Dihedral angles between the rings of Hoechst 33258 appear to change in a temperature-dependent manner. The drug/DNA complex is stabilized by single or bifurcated hydrogen bonds between the two N-H hydrogen-bond donors in the benzimidazole rings of Hoechst and adenine N3 and thymine O2 acceptors in the minor groove. A general preference for AT regions is conferred by electrostatic potential and by narrowing of the walls of the groove. Local point-by-point AT specificity follows from close van der Waals contacts between ring hydrogen atoms in Hoechst 33258 and the C2 hydrogens of adenines. Replacement of one benzimidazole ring by purine in a longer chain analogue of Hoechst 33258 could make that particular site GC tolerant in the manner observed at imidazole substitution for pyrrole in lexitropsins.

About this StructureAbout this Structure

1D45 is a Protein complex structure of sequences from [1] with and as ligands. Full crystallographic information is available from OCA.

ReferenceReference

Low-temperature crystallographic analyses of the binding of Hoechst 33258 to the double-helical DNA dodecamer C-G-C-G-A-A-T-T-C-G-C-G., Quintana JR, Lipanov AA, Dickerson RE, Biochemistry. 1991 Oct 22;30(42):10294-306. PMID:1718416

Page seeded by OCA on Thu Feb 21 12:12:47 2008

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OCA

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-[[Image:1d45.gif|left|200px]]<br /><applet load="1d45" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1d45.gif|left|200px]]<br /><applet load="1d45" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1d45, resolution 1.900&Aring;" />
 '''DNA DODECAMER C-G-C-G-A-A-T-T-C-G-C-G/HOECHST 33258 COMPLEX:-25 DEGREES C, PIPERAZINE DOWN'''<br />
 ==Overview==
-The crystal structure of the complex of Hoechst 33258 and the DNA, dodecamer C-G-C-G-A-A-T-T-C-G-C-G has been solved from X-ray data, collected at three different low temperatures (0, -25, and -100 degrees, C). Such temperatures have permitted collection of higher resolution data, (2.0, 1.9, and 2.0 A, respectively) than with previous X-ray studies of, the same complex. In all three cases, the drug is located in the narrow, central A-A-T-T region of the minor groove. Data analyses at -25 and -100, degrees C (each with a 1:1 drug/DNA ratio in the crystallizing solution), suggest a unique orientation for the drug. In contrast, two orientations, of the drug were found equally possible at 0 degrees C with a 2:1 drug/DNA, ratio in solution. Dihedral angles between the rings of Hoechst 33258, appear to change in a temperature-dependent manner. The drug/DNA complex, is stabilized by single or bifurcated hydrogen bonds between the two N-H, hydrogen-bond donors in the benzimidazole rings of Hoechst and adenine N3, and thymine O2 acceptors in the minor groove. A general preference for AT, regions is conferred by electrostatic potential and by narrowing of the, walls of the groove. Local point-by-point AT specificity follows from, close van der Waals contacts between ring hydrogen atoms in Hoechst 33258, and the C2 hydrogens of adenines. Replacement of one benzimidazole ring by, purine in a longer chain analogue of Hoechst 33258 could make that, particular site GC tolerant in the manner observed at imidazole, substitution for pyrrole in lexitropsins.
+The crystal structure of the complex of Hoechst 33258 and the DNA dodecamer C-G-C-G-A-A-T-T-C-G-C-G has been solved from X-ray data collected at three different low temperatures (0, -25, and -100 degrees C). Such temperatures have permitted collection of higher resolution data (2.0, 1.9, and 2.0 A, respectively) than with previous X-ray studies of the same complex. In all three cases, the drug is located in the narrow central A-A-T-T region of the minor groove. Data analyses at -25 and -100 degrees C (each with a 1:1 drug/DNA ratio in the crystallizing solution) suggest a unique orientation for the drug. In contrast, two orientations of the drug were found equally possible at 0 degrees C with a 2:1 drug/DNA ratio in solution. Dihedral angles between the rings of Hoechst 33258 appear to change in a temperature-dependent manner. The drug/DNA complex is stabilized by single or bifurcated hydrogen bonds between the two N-H hydrogen-bond donors in the benzimidazole rings of Hoechst and adenine N3 and thymine O2 acceptors in the minor groove. A general preference for AT regions is conferred by electrostatic potential and by narrowing of the walls of the groove. Local point-by-point AT specificity follows from close van der Waals contacts between ring hydrogen atoms in Hoechst 33258 and the C2 hydrogens of adenines. Replacement of one benzimidazole ring by purine in a longer chain analogue of Hoechst 33258 could make that particular site GC tolerant in the manner observed at imidazole substitution for pyrrole in lexitropsins.
 ==About this Structure==
-D45 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with HT and MG as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1D45 OCA].
+D45 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=HT:'>HT</scene> and <scene name='pdbligand=MG:'>MG</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D45 OCA].
 ==Reference==
 Low-temperature crystallographic analyses of the binding of Hoechst 33258 to the double-helical DNA dodecamer C-G-C-G-A-A-T-T-C-G-C-G., Quintana JR, Lipanov AA, Dickerson RE, Biochemistry. 1991 Oct 22;30(42):10294-306. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=1718416 1718416]
 [[Category: Protein complex]]
-[[Category: Dickerson, R.E.]]
+[[Category: Dickerson, R E.]]
-[[Category: Lipanov, A.A.]]
+[[Category: Lipanov, A A.]]
-[[Category: Quintana, J.R.]]
+[[Category: Quintana, J R.]]
 [[Category: HT]]
 [[Category: MG]]
@@ Line 21: / Line 21: @@
 [[Category: double helix]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 25 02:27:27 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:12:47 2008''