This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

207d

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

SOLUTION STRUCTURE OF MITHRAMYCIN DIMERS BOUND TO PARTIALLY OVERLAPPING SITES ON DNA

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/207d"

Categories: Large Structures | Synthetic construct | Fiala R | Patel DJ | Sastry M

@@ Line 1: / Line 1: @@
-[[Image:207d.jpg|left|200px]]<br /><applet load="207d" size="350" color="white" frame="true" align="right" spinBox="true"
-caption="207d" />
-'''SOLUTION STRUCTURE OF MITHRAMYCIN DIMERS BOUND TO PARTIALLY OVERLAPPING SITES ON DNA'''<br />
-==Overview==
+==SOLUTION STRUCTURE OF MITHRAMYCIN DIMERS BOUND TO PARTIALLY OVERLAPPING SITES ON DNA==
-Mithramycin (MTH) is a DNA-binding antitumor agent containing A-B, disaccharide and C-D-E trisaccharide segments projecting from opposite, ends of an aglycone chromophore. We have previously reported on the, solution structure of the MTH-DNA 6-mer complex based on a combined NMR, and molecular dynamics study. This study established that the, Mg(2+)-coordinated mithramycin dimer bound to a widened minor groove, centered about the sequence-specific (G-C).(G-C) site and that the C-D-E, trisaccharide segments from individual monomers were directed towards, opposite ends of the helix spanning a six base-pair segment. This research, is now extended to the binding of mithramycin dimers to partially, overlapping sites on the self-complementary d(T-A-G-C-T-A-G-C-T-A) 10-mer, duplex. The six base-pair mithramycin dimer footprint centered about, (G-C).(G-C) steps should result in a potential steric clash in the center, of the helix involving the inwardly pointing E-sugars of the pair of, mithramycin dimers bound to the DNA 10-mer duplex. The, MTH-d(T-A-G-C-T-A-G-C-T-A) complex (two MTH dimers per duplex) yields, narrow and well-resolved NMR spectra, which have been assigned to identify, intramolecular and intermolecular nuclear Overhauser enhancement (NOE), connectivities in the complex. The solution structure of the MTH-DNA, 10-mer complex based on distance-restrained molecular dynamics, calculations has defined the conformation of the drug and the DNA, necessary for accommodation of the pair of mithramycin dimers on the DNA, 10-mer helix. Specifically, the inwardly pointing E-sugars retain their, face-down alignment towards the floor of the minor groove and occupy, adjacent binding sites in the center of the duplex. This is achieved, in, part, through torsion angle differences in the glycosidic linkage bonds, along the length of the inwardly pointing aglycone-C-D-E trisaccharide, segment relative to its outwardly pointing aglycone-C-D-E trisaccharide, counterpart in the complex. In addition, a pronounced kink at the central, (T-A).(T-A) step opens the minor groove and generates additional space to, accommodate the inwardly pointing E-sugars at adjacent sites in the, MTH-DNA 10-mer complex. These studies establish conformational plasticity, in the C-D-E trisaccharide segment of the mithramycin dimer and, deformability of the DNA helix allowing mithramycin dimers to bind to, partially overlapping minor groove sites on the DNA helix.
+<StructureSection load='207d' size='340' side='right'caption='[[207d]]' scene=''>
+== Structural highlights ==
-==About this Structure==
+<table><tr><td colspan='2'>[[207d]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=207D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=207D FirstGlance]. <br>
-D is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=CRH:'>CRH</scene> and <scene name='pdbligand=MDA:'>MDA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=207D OCA].
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CRH:1,2-HYDRO-1-OXY-3,4-HYDRO-3-(1-METHOXY-2-OXY-3,4-DIHYDROXYPENTYL)-8,9-DIHYROXY-7-METHYLANTHRACENE'>CRH</scene>, <scene name='pdbligand=DDA:2,6-DIDEOXY-BETA-D-GLUCOSE'>DDA</scene>, <scene name='pdbligand=DDL:2,6-DIDEOXY-BETA-D-GALACTOSE'>DDL</scene>, <scene name='pdbligand=MDA:2,6-DIDEOXY-3+C-METHYL-D-RIBOPYRANOSIDE'>MDA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-==Reference==
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=207d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=207d OCA], [https://pdbe.org/207d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=207d RCSB], [https://www.ebi.ac.uk/pdbsum/207d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=207d ProSAT]</span></td></tr>
-Solution structure of mithramycin dimers bound to partially overlapping sites on DNA., Sastry M, Fiala R, Patel DJ, J Mol Biol. 1995 Sep 1;251(5):674-89. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=7666419 7666419]
+</table>
-[[Category: Protein complex]]
+__TOC__
-[[Category: Fiala, R.]]
+</StructureSection>
-[[Category: Patel, D.J.]]
+[[Category: Large Structures]]
-[[Category: Sastry, M.]]
+[[Category: Synthetic construct]]
-[[Category: CRH]]
+[[Category: Fiala R]]
-[[Category: MDA]]
+[[Category: Patel DJ]]
-[[Category: MG]]
+[[Category: Sastry M]]
-[[Category: dna]]
-[[Category: double helix]]
-[[Category: mithramycin]]
-[[Category: nmr]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jan 29 17:47:03 2008''

207d

From Proteopedia

Current revision

SOLUTION STRUCTURE OF MITHRAMYCIN DIMERS BOUND TO PARTIALLY OVERLAPPING SITES ON DNA

Structural highlights

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox