199d: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:199d.gif|left|200px]] | [[Image:199d.gif|left|200px]] | ||
'''SOLUTION STRUCTURE OF THE MONOALKYLATED MITOMYCIN C-DNA COMPLEX''' | {{Structure | ||
|PDB= 199d |SIZE=350|CAPTION= <scene name='initialview01'>199d</scene> | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=MOC:CARBAMIC ACID 2,6-DIAMINO-5-METHYL-4,7-DIOXO-2,3,4,7-TETRAHYDRO-1H-3A-AZA-CYCLOPENTA[A]INDEN-8-YLMETHYL ESTER'>MOC</scene> | |||
|ACTIVITY= | |||
|GENE= | |||
}} | |||
'''SOLUTION STRUCTURE OF THE MONOALKYLATED MITOMYCIN C-DNA COMPLEX''' | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
199D is a [ | 199D is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=199D OCA]. | ||
==Reference== | ==Reference== | ||
Solution structure of the monoalkylated mitomycin C-DNA complex., Sastry M, Fiala R, Lipman R, Tomasz M, Patel DJ, J Mol Biol. 1995 Mar 24;247(2):338-59. PMID:[http:// | Solution structure of the monoalkylated mitomycin C-DNA complex., Sastry M, Fiala R, Lipman R, Tomasz M, Patel DJ, J Mol Biol. 1995 Mar 24;247(2):338-59. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/7707379 7707379] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Fiala, R.]] | [[Category: Fiala, R.]] | ||
| Line 23: | Line 32: | ||
[[Category: nmr]] | [[Category: nmr]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 09:50:51 2008'' | ||
Revision as of 10:50, 20 March 2008
| |||||||
| Ligands: | |||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
SOLUTION STRUCTURE OF THE MONOALKYLATED MITOMYCIN C-DNA COMPLEX
OverviewOverview
Mitomycin C (MC) is a potent antitumor antibiotic which alkylates DNA through covalent linkage of its C-1" position with the exocyclic N2 amino group of guanine to yield the [MC]dG adduct at the duplex level. We report on the solution structure of the monoalkylated MC-DNA 9-mer complex where the [MC]dG5 adduct is positioned opposite dC14 in the d(A3-C4-[MC]G5-T6).d(A13-C14-G15-T16) sequence context. The solution structure was solved based on a combined NMR-molecular dynamics study including NOE intensity based refinement. The formation of the [MC]dG adduct occurs with retention of the Watson-Crick alignment at the [MC]dG5.dC14 base-pair and flanking pairs in the complex. The MC ring is positioned in the minor groove with its indoloquinone aromatic ring system at a approximately 45 degrees angle relative to the helix axis and directed towards the 3'-direction on the unmodified strand. The MC indoloquinone chromophore is asymmetrically positioned in a slightly widened minor groove so that its plane is parallel to and stacked over the d(C14-G15-T16) segment on the unmodified strand with its other face exposed to solvent. The MC five-membered ring adopts an envelope pucker with its C-2" atom displaced from the mean plane and directed away from the unmodified strand. We observe conformational perturbations in the DNA 9-mer duplex on formation of the monoalkylated MC complex. Specifically, the base-pairs are displaced by approximately -3.0 A towards the major groove on positioning the MC in the minor groove. This perturbation is accompanied by base stacking patterns similar to those observed in A-DNA while the majority of the sugars adopt puckers characteristic of B-DNA. Conformational perturbations as monitored by helix twist, sugar pucker pseudorotation and glycosidic torsion angles are also observed for the d(T6-C7-I8).d(C11-G12-A13) segment that is adjacent to but does not overlap the MC binding on the 9-mer duplex. We note that the O-10" atom on the carbamate side-chain of MC forms an intermolecular hydrogen bond with the exocyclic amino group of dG15 in two of the three refined structures of the complex. The solution structure of the complex containing this intramolecular hydrogen bond readily explains both the previously observed d(C-G).d(C-G) sequence requirement for cross-linking and the observed, somewhat less stringent, requirement of the same sequence for the initial monoalkylation step.(ABSTRACT TRUNCATED AT 400 WORDS)
About this StructureAbout this Structure
199D is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.
ReferenceReference
Solution structure of the monoalkylated mitomycin C-DNA complex., Sastry M, Fiala R, Lipman R, Tomasz M, Patel DJ, J Mol Biol. 1995 Mar 24;247(2):338-59. PMID:7707379
Page seeded by OCA on Thu Mar 20 09:50:51 2008