1dsa
From Proteopedia
(New page: 200px<br /><applet load="1dsa" size="450" color="white" frame="true" align="right" spinBox="true" caption="1dsa" /> '''(+)-DUOCARMYCIN SA COVALENTLY LINKED TO DUPL...) |
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| - | [[Image:1dsa.gif|left|200px]]<br /><applet load="1dsa" size=" | + | [[Image:1dsa.gif|left|200px]]<br /><applet load="1dsa" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1dsa" /> | caption="1dsa" /> | ||
'''(+)-DUOCARMYCIN SA COVALENTLY LINKED TO DUPLEX DNA, NMR, 20 STRUCTURES'''<br /> | '''(+)-DUOCARMYCIN SA COVALENTLY LINKED TO DUPLEX DNA, NMR, 20 STRUCTURES'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The three-dimensional solution structure of duocarmycin SA in complex with | + | The three-dimensional solution structure of duocarmycin SA in complex with d-(G1ACTAATTGAC11).d-(G12TCATTAGTC22) has been determined by restrained molecular dynamics and relaxation matrix calculations using experimental NOE distance and torsion angle constraints derived from 1H NMR spectroscopy. The final input data consisted of a total of 858 distance and 189 dihedral angle constraints, an average of 46 constraints per residue. In the ensemble of 20 final structures, there were no distance constraint violations >0.06 A or torsion angle violations >0.8 degrees. The average pairwise root mean square deviation (RMSD) over all 20 structures for the binding site region is 0.57 A (average RMSD from the mean: 0.39 A). Although the DNA is very B-like, the sugar-phosphate backbone torsion angles beta, epsilon, and zeta are distorted from standard values in the binding site region. The structure reveals site-specific bonding of duocarmycin SA at the N3 position of adenine 19 in the AT-rich minor groove of the duplex and binding stabilization via hydrophobic interactions. Comparisons have been made to the structure of a closely related complex of duocarmycin A bound to an AT-rich DNA duplex. These results provide insights into critical aspects of the alkylation site selectivity and source of catalysis of the DNA alkylating agents, and the unusual stability of the resulting adducts. |
==About this Structure== | ==About this Structure== | ||
| - | 1DSA is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with DSA as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1DSA is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=DSA:'>DSA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DSA OCA]. |
==Reference== | ==Reference== | ||
High resolution solution structure of a DNA duplex alkylated by the antitumor agent duocarmycin SA., Eis PS, Smith JA, Rydzewski JM, Case DA, Boger DL, Chazin WJ, J Mol Biol. 1997 Sep 19;272(2):237-52. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9299351 9299351] | High resolution solution structure of a DNA duplex alkylated by the antitumor agent duocarmycin SA., Eis PS, Smith JA, Rydzewski JM, Case DA, Boger DL, Chazin WJ, J Mol Biol. 1997 Sep 19;272(2):237-52. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9299351 9299351] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Case, D | + | [[Category: Case, D A.]] |
| - | [[Category: Chazin, W | + | [[Category: Chazin, W J.]] |
| - | [[Category: Eis, P | + | [[Category: Eis, P S.]] |
| - | [[Category: Smith, J | + | [[Category: Smith, J A.]] |
[[Category: DSA]] | [[Category: DSA]] | ||
[[Category: antitumor agent]] | [[Category: antitumor agent]] | ||
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[[Category: minor groove binding]] | [[Category: minor groove binding]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:19:55 2008'' |
Revision as of 10:19, 21 February 2008
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(+)-DUOCARMYCIN SA COVALENTLY LINKED TO DUPLEX DNA, NMR, 20 STRUCTURES
Overview
The three-dimensional solution structure of duocarmycin SA in complex with d-(G1ACTAATTGAC11).d-(G12TCATTAGTC22) has been determined by restrained molecular dynamics and relaxation matrix calculations using experimental NOE distance and torsion angle constraints derived from 1H NMR spectroscopy. The final input data consisted of a total of 858 distance and 189 dihedral angle constraints, an average of 46 constraints per residue. In the ensemble of 20 final structures, there were no distance constraint violations >0.06 A or torsion angle violations >0.8 degrees. The average pairwise root mean square deviation (RMSD) over all 20 structures for the binding site region is 0.57 A (average RMSD from the mean: 0.39 A). Although the DNA is very B-like, the sugar-phosphate backbone torsion angles beta, epsilon, and zeta are distorted from standard values in the binding site region. The structure reveals site-specific bonding of duocarmycin SA at the N3 position of adenine 19 in the AT-rich minor groove of the duplex and binding stabilization via hydrophobic interactions. Comparisons have been made to the structure of a closely related complex of duocarmycin A bound to an AT-rich DNA duplex. These results provide insights into critical aspects of the alkylation site selectivity and source of catalysis of the DNA alkylating agents, and the unusual stability of the resulting adducts.
About this Structure
1DSA is a Protein complex structure of sequences from [1] with as ligand. Full crystallographic information is available from OCA.
Reference
High resolution solution structure of a DNA duplex alkylated by the antitumor agent duocarmycin SA., Eis PS, Smith JA, Rydzewski JM, Case DA, Boger DL, Chazin WJ, J Mol Biol. 1997 Sep 19;272(2):237-52. PMID:9299351
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