1vrl

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(New page: 200px<br /><applet load="1vrl" size="450" color="white" frame="true" align="right" spinBox="true" caption="1vrl, resolution 2.50&Aring;" /> '''MutY adenine glycosy...)
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[[Image:1vrl.gif|left|200px]]<br /><applet load="1vrl" size="450" color="white" frame="true" align="right" spinBox="true"
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[[Image:1vrl.gif|left|200px]]<br /><applet load="1vrl" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1vrl, resolution 2.50&Aring;" />
caption="1vrl, resolution 2.50&Aring;" />
'''MutY adenine glycosylase in complex with DNA and soaked adenine free base'''<br />
'''MutY adenine glycosylase in complex with DNA and soaked adenine free base'''<br />
==Overview==
==Overview==
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The genomes of aerobic organisms suffer chronic oxidation of guanine to, the genotoxic product 8-oxoguanine (oxoG). Replicative DNA polymerases, misread oxoG residues and insert adenine instead of cytosine opposite the, oxidized base. Both bases in the resulting A*oxoG mispair are mutagenic, lesions, and both must undergo base-specific replacement to restore the, original C*G pair. Doing so represents a formidable challenge to the DNA, repair machinery, because adenine makes up roughly 25% of the bases in, most genomes. The evolutionarily conserved enzyme adenine DNA glycosylase, (called MutY in bacteria and hMYH in humans) initiates repair of A*oxoG to, C*G by removing the inappropriately paired adenine base from the DNA, backbone. A central issue concerning MutY function is the mechanism by, which A*oxoG mispairs are targeted among the vast excess of A*T pairs., Here we report the use of disulphide crosslinking to obtain, high-resolution crystal structures of MutY-DNA lesion-recognition, complexes. These structures reveal the basis for recognizing both lesions, in the A*oxoG pair and for catalysing removal of the adenine base.
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The genomes of aerobic organisms suffer chronic oxidation of guanine to the genotoxic product 8-oxoguanine (oxoG). Replicative DNA polymerases misread oxoG residues and insert adenine instead of cytosine opposite the oxidized base. Both bases in the resulting A*oxoG mispair are mutagenic lesions, and both must undergo base-specific replacement to restore the original C*G pair. Doing so represents a formidable challenge to the DNA repair machinery, because adenine makes up roughly 25% of the bases in most genomes. The evolutionarily conserved enzyme adenine DNA glycosylase (called MutY in bacteria and hMYH in humans) initiates repair of A*oxoG to C*G by removing the inappropriately paired adenine base from the DNA backbone. A central issue concerning MutY function is the mechanism by which A*oxoG mispairs are targeted among the vast excess of A*T pairs. Here we report the use of disulphide crosslinking to obtain high-resolution crystal structures of MutY-DNA lesion-recognition complexes. These structures reveal the basis for recognizing both lesions in the A*oxoG pair and for catalysing removal of the adenine base.
==About this Structure==
==About this Structure==
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1VRL is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Geobacillus_stearothermophilus Geobacillus stearothermophilus] with CA, SF4 and ADE as [http://en.wikipedia.org/wiki/ligands ligands]. This structure superseeds the now removed PDB entry 1RRT. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1VRL OCA].
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1VRL is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Geobacillus_stearothermophilus Geobacillus stearothermophilus] with <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=SF4:'>SF4</scene> and <scene name='pdbligand=ADE:'>ADE</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. This structure supersedes the now removed PDB entry 1RRT. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VRL OCA].
==Reference==
==Reference==
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[[Category: Protein complex]]
[[Category: Protein complex]]
[[Category: Banerjee, A.]]
[[Category: Banerjee, A.]]
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[[Category: Fromme, J.C.]]
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[[Category: Fromme, J C.]]
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[[Category: Huang, S.J.]]
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[[Category: Huang, S J.]]
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[[Category: Verdine, G.L.]]
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[[Category: Verdine, G L.]]
[[Category: ADE]]
[[Category: ADE]]
[[Category: CA]]
[[Category: CA]]
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[[Category: protein-dna complex]]
[[Category: protein-dna complex]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sat Nov 24 23:06:11 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:37:58 2008''

Revision as of 13:37, 21 February 2008


1vrl, resolution 2.50Å

Drag the structure with the mouse to rotate

MutY adenine glycosylase in complex with DNA and soaked adenine free base

Overview

The genomes of aerobic organisms suffer chronic oxidation of guanine to the genotoxic product 8-oxoguanine (oxoG). Replicative DNA polymerases misread oxoG residues and insert adenine instead of cytosine opposite the oxidized base. Both bases in the resulting A*oxoG mispair are mutagenic lesions, and both must undergo base-specific replacement to restore the original C*G pair. Doing so represents a formidable challenge to the DNA repair machinery, because adenine makes up roughly 25% of the bases in most genomes. The evolutionarily conserved enzyme adenine DNA glycosylase (called MutY in bacteria and hMYH in humans) initiates repair of A*oxoG to C*G by removing the inappropriately paired adenine base from the DNA backbone. A central issue concerning MutY function is the mechanism by which A*oxoG mispairs are targeted among the vast excess of A*T pairs. Here we report the use of disulphide crosslinking to obtain high-resolution crystal structures of MutY-DNA lesion-recognition complexes. These structures reveal the basis for recognizing both lesions in the A*oxoG pair and for catalysing removal of the adenine base.

About this Structure

1VRL is a Protein complex structure of sequences from Geobacillus stearothermophilus with , and as ligands. This structure supersedes the now removed PDB entry 1RRT. Full crystallographic information is available from OCA.

Reference

Structural basis for removal of adenine mispaired with 8-oxoguanine by MutY adenine DNA glycosylase., Fromme JC, Banerjee A, Huang SJ, Verdine GL, Nature. 2004 Feb 12;427(6975):652-6. PMID:14961129

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