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144d

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MINOR GROOVE BINDING OF SN6999 TO AN ALKYLATED DNA: MOLECULAR STRUCTURE OF D(CGC[E6G]AATTCGCG)-SN6999 COMPLEX

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Retrieved from "http://52.214.119.220/wiki/index.php/144d"

Categories: Large Structures | Denny WA | Gao Y-G | Sriram M | Wang AH-J

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-[[Image:144d.jpg|left|200px]]<br /><applet load="144d" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="144d, resolution 2.250&Aring;" />
-'''MINOR GROOVE BINDING OF SN6999 TO AN ALKYLATED DNA: MOLECULAR STRUCTURE OF D(CGC[E6G]AATTCGCG)-SN6999 COMPLEX'''<br />
-==Overview==
+==MINOR GROOVE BINDING OF SN6999 TO AN ALKYLATED DNA: MOLECULAR STRUCTURE OF D(CGC[E6G]AATTCGCG)-SN6999 COMPLEX==
-The interaction between a potent synthetic antitumor and antiviral minor, groove binding drug, 1-methyl-4-[4-[4-(4-(1-methylquinolinium)amino)benzamido]anilino], pyridinium dichloride (SN6999) and an alkylated DNA d(CGC[e6G]AATTCGCG), dodecamer has been studied by X-ray crystallography. The complex forms a, new crystal lattice in the space group P2(1)2(1)2(1) with unit cell, dimensions of a = 28.48 A, b = 36.11 A, and c = 69.60 A. The structure has, been solved by the molecular replacement method and refined to an R-factor, of 17.0% at approximately 2.5 A resolution using 1618 reflections. In the, complex, the SN6999 covers almost six base pairs in the narrow minor, groove with the 1-methylquinolinium (Q) ring near T8-A17 and the, 1-methylpyridinium (P) ring near the C3-G22 base pair. The central, benzamido (BQ) and anilino (BP) rings are essentially coplanar, with the Q, and P rings having large dihedral angles of 38 degrees and 39 degrees, respectively, to the plane of BQ/BP. There is only one direct hydrogen, bond between the amide NH of SN6999 to T20O2 of DNA. The drug-DNA, interaction is stabilized by stacking interaction of sugar oxygens from, T20O4' to BQ and C21O4' to BP. There is charge-induced dipole interaction, between the positively charged nitrogen atom of 1-methylquinolinium with, C9O4' and that of 1-methylpyridinium with G22O4'. The crystal structure of, the complex can be used to explain the NMR results. SN6999 lacks the, crescent shape observed in other minor groove binding drugs and distorts, the DNA duplex upon binding. The complex packs in the lattice using the, G-N2:G-N3 interlocking base pairs at both ends of the helix. As in earlier, cases, the two independent e6G:C base pairs adopt different base pairing, schemes. The e6G16:C9 base pair adopts a previously observed bifurcated, configuration involving three-centered hydrogen bonds and is similar to a, Watson-Crick pairing. In contrast, the e6G4:C21 base pair adopts a novel, "reverse wobble" configuration with C21 being pushed toward the major, groove side. The ethyl group is in the proximal orientation (to N7) in, both base pairs. Taken together with the observations found in the same, DNA complexed to Hoechst 33258, Hoechst 33342, and retropsin from, different crystal lattices, the results suggest that the e6G:C base, pairing is weak and polymorphic when compared to a normal G:C base pair, and the DNA duplex containing this lesion is readily distorted.
+<StructureSection load='144d' size='340' side='right'caption='[[144d]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
+== Structural highlights ==
-==About this Structure==
+<table><tr><td colspan='2'>[[144d]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=144D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=144D FirstGlance]. <br>
-D is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with SN6 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=144D 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]] 2.25&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=G36:O6-ETHYL-2-DEOXYGUANOSINE-5-MONOPHOSPHATE'>G36</scene>, <scene name='pdbligand=SN6:1-METHYL-4-[4-[4-(4-(1-METHYLQUINOLINIUM)AMINO)BENZAMIDO]ANILINO]PYRIDINIUM'>SN6</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=144d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=144d OCA], [https://pdbe.org/144d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=144d RCSB], [https://www.ebi.ac.uk/pdbsum/144d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=144d ProSAT]</span></td></tr>
-Minor groove binding of SN6999 to an alkylated DNA: molecular structure of d(CGC[e6G]AATTCGCG)-SN6999 complex., Gao YG, Sriram M, Denny WA, Wang AH, Biochemistry. 1993 Sep 21;32(37):9639-48. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=8373768 8373768]
+</table>
-[[Category: Protein complex]]
+__TOC__
-[[Category: Denny, W.A.]]
+</StructureSection>
-[[Category: Gao, Y.G.]]
+[[Category: Large Structures]]
-[[Category: Sriram, M.]]
+[[Category: Denny WA]]
-[[Category: Wang, A.H.J.]]
+[[Category: Gao Y-G]]
-[[Category: SN6]]
+[[Category: Sriram M]]
-[[Category: b-dna]]
+[[Category: Wang AH-J]]
-[[Category: complexed with drug]]
-[[Category: double helix]]
-[[Category: modified]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sat Nov 24 21:55:41 2007''

144d

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MINOR GROOVE BINDING OF SN6999 TO AN ALKYLATED DNA: MOLECULAR STRUCTURE OF D(CGC[E6G]AATTCGCG)-SN6999 COMPLEX

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