107d: Difference between revisions
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'''SOLUTION STRUCTURE OF THE COVALENT DUOCARMYCIN A-DNA DUPLEX COMPLEX'''<br /> | '''SOLUTION STRUCTURE OF THE COVALENT DUOCARMYCIN A-DNA DUPLEX COMPLEX'''<br /> | ||
==Overview== | ==Overview== | ||
Duocarmycin A is an antitumour antibiotic that binds covalently to the | Duocarmycin A is an antitumour antibiotic that binds covalently to the minor groove N-3 position of adenine with sequence specificity for the 3'-adenine in a d(A-A-A-A) tract in duplex DNA. The adenine ring becomes protonated on duocarmycin adduct formation resulting in charge delocalization over the purine ring system. We report on the solution structure of duocarmycin A bound site specifically to A12 (designated *A12+) in the sequence context d(T3-T4-T5-T6).d(A9-A10-A11-*A12+) within a hairpin duplex. The solution structure was solved based on a combined NMR-molecular dynamics study including NOE based intensity refinement. The A and B-rings of duocarmycin are positioned deep within the walls of the minor groove with the B-ring (which is furthest from the covalent linkage site) directed towards the 5'-end of the modified strand. Duocarmycin adopts an extended conformation and is aligned at approximately 45 degrees to the helix axis with its non-polar concave edges interacting with the floor of the minor groove while its polar edges are sandwiched within the walls of the minor groove. The T3.*A12+ modification site pair forms a weak central Watson-Crick hydrogen bond in contrast to all A.T and G.C pairs, which align through standard Watson-Crick pairing in the complex. The helical parameters are consistent with a minimally perturbed right-handed duplex in the complex with minor groove width and x-displacement parameters indicative of a B-form helix. A striking feature of the complex is the positioning of duocarmycin A within the walls of the minor groove resulting in upfield shifts of the minor groove sugar protons, as well as backbone proton and phosphorus resonances in the DNA segment spanning the binding site. | ||
==About this Structure== | ==About this Structure== | ||
107D is a | 107D is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=DUO:'>DUO</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=107D OCA]. | ||
==Reference== | ==Reference== | ||
Solution structure of the covalent duocarmycin A-DNA duplex complex., Lin CH, Patel DJ, J Mol Biol. 1995 Apr 21;248(1):162-79. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=7731041 7731041] | Solution structure of the covalent duocarmycin A-DNA duplex complex., Lin CH, Patel DJ, J Mol Biol. 1995 Apr 21;248(1):162-79. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=7731041 7731041] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Lin, C | [[Category: Lin, C H.]] | ||
[[Category: Patel, D | [[Category: Patel, D J.]] | ||
[[Category: DUO]] | [[Category: DUO]] | ||
[[Category: dna]] | [[Category: dna]] | ||
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[[Category: nmr]] | [[Category: nmr]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:37:23 2008'' | ||
Revision as of 12:37, 21 February 2008
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SOLUTION STRUCTURE OF THE COVALENT DUOCARMYCIN A-DNA DUPLEX COMPLEX
OverviewOverview
Duocarmycin A is an antitumour antibiotic that binds covalently to the minor groove N-3 position of adenine with sequence specificity for the 3'-adenine in a d(A-A-A-A) tract in duplex DNA. The adenine ring becomes protonated on duocarmycin adduct formation resulting in charge delocalization over the purine ring system. We report on the solution structure of duocarmycin A bound site specifically to A12 (designated *A12+) in the sequence context d(T3-T4-T5-T6).d(A9-A10-A11-*A12+) within a hairpin duplex. The solution structure was solved based on a combined NMR-molecular dynamics study including NOE based intensity refinement. The A and B-rings of duocarmycin are positioned deep within the walls of the minor groove with the B-ring (which is furthest from the covalent linkage site) directed towards the 5'-end of the modified strand. Duocarmycin adopts an extended conformation and is aligned at approximately 45 degrees to the helix axis with its non-polar concave edges interacting with the floor of the minor groove while its polar edges are sandwiched within the walls of the minor groove. The T3.*A12+ modification site pair forms a weak central Watson-Crick hydrogen bond in contrast to all A.T and G.C pairs, which align through standard Watson-Crick pairing in the complex. The helical parameters are consistent with a minimally perturbed right-handed duplex in the complex with minor groove width and x-displacement parameters indicative of a B-form helix. A striking feature of the complex is the positioning of duocarmycin A within the walls of the minor groove resulting in upfield shifts of the minor groove sugar protons, as well as backbone proton and phosphorus resonances in the DNA segment spanning the binding site.
About this StructureAbout this Structure
107D is a Protein complex structure of sequences from [1] with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Solution structure of the covalent duocarmycin A-DNA duplex complex., Lin CH, Patel DJ, J Mol Biol. 1995 Apr 21;248(1):162-79. PMID:7731041
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