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.

334d

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

DEFINING GC-SPECIFICITY IN THE MINOR GROOVE: SIDE-BY-SIDE BINDING OF THE DI-IMIDAZOLE LEXITROPSIN TO C-A-T-G-G-C-C-A-T-G

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/334d"

Categories: Large Structures | Dickerson RE | Goodsell DS | Kopka ML

@@ Line 1: / Line 1: @@
-[[Image:334d.gif|left|200px]]<br /><applet load="334d" size="350" color="white" frame="true" align="right" spinBox="true"
-caption="334d, resolution 1.800&Aring;" />
-'''DEFINING GC-SPECIFICITY IN THE MINOR GROOVE: SIDE-BY-SIDE BINDING OF THE DI-IMIDAZOLE LEXITROPSIN TO C-A-T-G-G-C-C-A-T-G'''<br />
-==Overview==
+==DEFINING GC-SPECIFICITY IN THE MINOR GROOVE: SIDE-BY-SIDE BINDING OF THE DI-IMIDAZOLE LEXITROPSIN TO C-A-T-G-G-C-C-A-T-G==
-BACKGROUND: Polyamide drugs, such as netropsin, distamycin and their, lexitropsin derivatives, can be inserted into a narrow B-DNA minor groove, to form 1:1 complexes that can distinguish AT base pairs from GC, but, cannot detect end-for-end base-pair reversals such as TA for AT. In, contrast, 2:1 side-by-side polyamide drug complexes potentially are, capable of such discrimination. Imidazole (Im) and pyrrole (Py) rings, side-by-side read a GC base pair with the Im ring recognizing the guanine, side. But the reason for this specific G-Im association is unclear because, the guanine NH2 group sits in the center of the groove. A 2:1 drug:DNA, complex that presents Im at both ends of a GC base pair should help, unscramble the issue of imidazole reading specificity. RESULTS: We have, determined the crystal structure of a 2:1 complex of a di-imidazole, lexitropsin (DIM), an analogue of distamycin, and a DNA decamer with the, sequence C-A-T-G-G-C-C-A-T-G. The two DIM molecules sit antiparallel to, one another in a broad minor groove, with their cationic tails widely, separated. Im rings of one drug molecule stack against amide groups of the, other. DIM1 rests against nucleotides C7A8T9G10 of strand 1 of the helix, whereas DIM2 rests against G14G15C16C17 on strand 2. All DIM amide, nitrogens donate hydrogen bonds to N and O atoms on the floor of the DNA, groove and, in addition, the two Im rings on DIM2 accept hydrogen bonds, from guanine N2 amines, thereby providing specific reading. The guanine N2, amine can bond to Im on its own side of the groove, but not on the, cytosine side, because of limits on close approach of the two Im rings and, the geometry of sp2 hybridization about the amide nitrogen. CONCLUSIONS:, Im and Py rings distinguish AT from GC base pairs because of steric, factors involving the bulk of the guanine amine, and the ability of Im to, form a hydrogen bond with the amine. Side-by-side Im and Py rings, differentiate GC from CG base pairs because of tight steric contacts and, sp2 hybridization at the amine nitrogen atom, with the favored, conformations being G/Im,Py/C and C/Py,Im/G. Discrimination between AT and, TA base pairs may be possible using bulkier rings, such as thiazole to, select the A end of the base pair.
+<StructureSection load='334d' size='340' side='right'caption='[[334d]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
+== Structural highlights ==
-==About this Structure==
+<table><tr><td colspan='2'>[[334d]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=334D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=334D 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=DIM:'>DIM</scene> and <scene name='pdbligand=CA:'>CA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=334D OCA].
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DIM:DIIMIDAZOLE+LEXITROPSIN'>DIM</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=334d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=334d OCA], [https://pdbe.org/334d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=334d RCSB], [https://www.ebi.ac.uk/pdbsum/334d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=334d ProSAT]</span></td></tr>
-Defining GC-specificity in the minor groove: side-by-side binding of the di-imidazole lexitropsin to C-A-T-G-G-C-C-A-T-G., Kopka ML, Goodsell DS, Han GW, Chiu TK, Lown JW, Dickerson RE, Structure. 1997 Aug 15;5(8):1033-46. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9309219 9309219]
+</table>
-[[Category: Protein complex]]
+__TOC__
-[[Category: Dickerson, R.E.]]
+</StructureSection>
-[[Category: Goodsell, D.S.]]
+[[Category: Large Structures]]
-[[Category: Kopka, M.L.]]
+[[Category: Dickerson RE]]
-[[Category: CA]]
+[[Category: Goodsell DS]]
-[[Category: DIM]]
+[[Category: Kopka ML]]
-[[Category: b-dna]]
-[[Category: double helix]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jan 29 21:35:42 2008''

334d

From Proteopedia

Current revision

DEFINING GC-SPECIFICITY IN THE MINOR GROOVE: SIDE-BY-SIDE BINDING OF THE DI-IMIDAZOLE LEXITROPSIN TO C-A-T-G-G-C-C-A-T-G

Structural highlights

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox