2a5p: Difference between revisions

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==Overview==

It has been widely accepted that DNA can adopt other biologically relevant, structures beside the Watson-Crick double helix. One recent important, example is the guanine-quadruplex (G-quadruplex) structure formed by, guanine tracts found in the MYC (or c-myc) promoter region, which, regulates the transcription of the MYC oncogene. Stabilization of this, G-quadruplex by ligands, such as the cationic porphyrin TMPyP4, decreases, the transcriptional level of MYC. Here, we report the first structure of a, DNA fragment containing five guanine tracts from this region. An unusual, G-quadruplex fold, which was derived from NMR restraints using unambiguous, model-independent resonance assignment approaches, involves a core of, three stacked guanine tetrads formed by four parallel guanine tracts with, all anti guanines and a snapback 3'-end syn guanine. We have determined, the structure of the complex formed between this G-quadruplex and TMPyP4., This structural information, combined with details of small-molecule, interaction, provides a platform for the design of anticancer drugs, targeting multi-guanine-tract sequences that are found in the MYC and, other oncogenic promoters, as well as in telomeres.

It has been widely accepted that DNA can adopt other biologically relevant structures beside the Watson-Crick double helix. One recent important example is the guanine-quadruplex (G-quadruplex) structure formed by guanine tracts found in the MYC (or c-myc) promoter region, which regulates the transcription of the MYC oncogene. Stabilization of this G-quadruplex by ligands, such as the cationic porphyrin TMPyP4, decreases the transcriptional level of MYC. Here, we report the first structure of a DNA fragment containing five guanine tracts from this region. An unusual G-quadruplex fold, which was derived from NMR restraints using unambiguous model-independent resonance assignment approaches, involves a core of three stacked guanine tetrads formed by four parallel guanine tracts with all anti guanines and a snapback 3'-end syn guanine. We have determined the structure of the complex formed between this G-quadruplex and TMPyP4. This structural information, combined with details of small-molecule interaction, provides a platform for the design of anticancer drugs targeting multi-guanine-tract sequences that are found in the MYC and other oncogenic promoters, as well as in telomeres.

==About this Structure==

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[[Category: Homo sapiens]]

[[Category: Protein complex]]

[[Category: Gaw, H.Y.]]

[[Category: Gaw, H Y.]]

[[Category: Kuryavyi, V.V.]]

[[Category: Kuryavyi, V V.]]

[[Category: Patel, D.J.]]

[[Category: Patel, D J.]]

[[Category: Phan, A.T.]]

[[Category: Phan, A T.]]

[[Category: monomeric parallel-stranded quadruplex; c-myc promoter 3+1 g-tetrad; single nucleotide chain reversal loop; gag triad; gaag loop]]

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@@ Line 4: / Line 4: @@
 ==Overview==
-It has been widely accepted that DNA can adopt other biologically relevant, structures beside the Watson-Crick double helix. One recent important, example is the guanine-quadruplex (G-quadruplex) structure formed by, guanine tracts found in the MYC (or c-myc) promoter region, which, regulates the transcription of the MYC oncogene. Stabilization of this, G-quadruplex by ligands, such as the cationic porphyrin TMPyP4, decreases, the transcriptional level of MYC. Here, we report the first structure of a, DNA fragment containing five guanine tracts from this region. An unusual, G-quadruplex fold, which was derived from NMR restraints using unambiguous, model-independent resonance assignment approaches, involves a core of, three stacked guanine tetrads formed by four parallel guanine tracts with, all anti guanines and a snapback 3'-end syn guanine. We have determined, the structure of the complex formed between this G-quadruplex and TMPyP4., This structural information, combined with details of small-molecule, interaction, provides a platform for the design of anticancer drugs, targeting multi-guanine-tract sequences that are found in the MYC and, other oncogenic promoters, as well as in telomeres.
+It has been widely accepted that DNA can adopt other biologically relevant structures beside the Watson-Crick double helix. One recent important example is the guanine-quadruplex (G-quadruplex) structure formed by guanine tracts found in the MYC (or c-myc) promoter region, which regulates the transcription of the MYC oncogene. Stabilization of this G-quadruplex by ligands, such as the cationic porphyrin TMPyP4, decreases the transcriptional level of MYC. Here, we report the first structure of a DNA fragment containing five guanine tracts from this region. An unusual G-quadruplex fold, which was derived from NMR restraints using unambiguous model-independent resonance assignment approaches, involves a core of three stacked guanine tetrads formed by four parallel guanine tracts with all anti guanines and a snapback 3'-end syn guanine. We have determined the structure of the complex formed between this G-quadruplex and TMPyP4. This structural information, combined with details of small-molecule interaction, provides a platform for the design of anticancer drugs targeting multi-guanine-tract sequences that are found in the MYC and other oncogenic promoters, as well as in telomeres.
 ==About this Structure==
@@ Line 13: / Line 13: @@
 [[Category: Homo sapiens]]
 [[Category: Protein complex]]
-[[Category: Gaw, H.Y.]]
+[[Category: Gaw, H Y.]]
-[[Category: Kuryavyi, V.V.]]
+[[Category: Kuryavyi, V V.]]
-[[Category: Patel, D.J.]]
+[[Category: Patel, D J.]]
-[[Category: Phan, A.T.]]
+[[Category: Phan, A T.]]
 [[Category: monomeric parallel-stranded quadruplex; c-myc promoter 3+1 g-tetrad; single nucleotide chain reversal loop; gag triad; gaag loop]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jan 29 17:54:57 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:23:52 2008''