1zgw

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(New page: 200px<br /><applet load="1zgw" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zgw" /> '''NMR structure of E. Coli Ada protein in comp...)
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[[Image:1zgw.gif|left|200px]]<br /><applet load="1zgw" size="450" color="white" frame="true" align="right" spinBox="true"
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[[Image:1zgw.gif|left|200px]]<br /><applet load="1zgw" size="350" color="white" frame="true" align="right" spinBox="true"
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'''NMR structure of E. Coli Ada protein in complex with DNA'''<br />
'''NMR structure of E. Coli Ada protein in complex with DNA'''<br />
==Overview==
==Overview==
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The transcriptional activity of many sequence-specific DNA binding, proteins is directly regulated by posttranslational covalent modification., Although this form of regulation was first described nearly two decades, ago, it remains poorly understood at a mechanistic level. The prototype, for a transcription factor controlled by posttranslational modification is, E. coli Ada protein, a chemosensor that both repairs methylation damage in, DNA and coordinates the resistance response to genotoxic methylating, agents. Ada repairs methyl phosphotriester lesions in DNA by transferring, the aberrant methyl group to one of its own cysteine residues; this, site-specific methylation enhances tremendously the DNA binding activity, of the protein, thereby enabling it to activate a methylation-resistance, regulon. Here, we report solution and X-ray structures of the, Cys-methylated chemosensor domain of Ada bound to DNA. The structures, reveal that both phosphotriester repair and methylation-dependent, transcriptional activation function through a zinc- and, methylation-dependent electrostatic switch.
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The transcriptional activity of many sequence-specific DNA binding proteins is directly regulated by posttranslational covalent modification. Although this form of regulation was first described nearly two decades ago, it remains poorly understood at a mechanistic level. The prototype for a transcription factor controlled by posttranslational modification is E. coli Ada protein, a chemosensor that both repairs methylation damage in DNA and coordinates the resistance response to genotoxic methylating agents. Ada repairs methyl phosphotriester lesions in DNA by transferring the aberrant methyl group to one of its own cysteine residues; this site-specific methylation enhances tremendously the DNA binding activity of the protein, thereby enabling it to activate a methylation-resistance regulon. Here, we report solution and X-ray structures of the Cys-methylated chemosensor domain of Ada bound to DNA. The structures reveal that both phosphotriester repair and methylation-dependent transcriptional activation function through a zinc- and methylation-dependent electrostatic switch.
==About this Structure==
==About this Structure==
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1ZGW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1ZGW OCA].
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1ZGW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZGW OCA].
==Reference==
==Reference==
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[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Doetsch, V.]]
[[Category: Doetsch, V.]]
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[[Category: Gross, J.D.]]
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[[Category: Gross, J D.]]
[[Category: He, C.]]
[[Category: He, C.]]
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[[Category: Hus, J.C.]]
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[[Category: Hus, J C.]]
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[[Category: Lane, W.S.]]
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[[Category: Lane, W S.]]
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[[Category: Norman, D.P.]]
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[[Category: Norman, D P.]]
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[[Category: Sun, L.J.]]
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[[Category: Sun, L J.]]
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[[Category: Verdine, G.L.]]
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[[Category: Verdine, G L.]]
[[Category: Wagner, G.]]
[[Category: Wagner, G.]]
[[Category: Wei, H.]]
[[Category: Wei, H.]]
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[[Category: zinc ligand]]
[[Category: zinc ligand]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 07:26:41 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:15:23 2008''

Revision as of 14:15, 21 February 2008


1zgw

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NMR structure of E. Coli Ada protein in complex with DNA

Overview

The transcriptional activity of many sequence-specific DNA binding proteins is directly regulated by posttranslational covalent modification. Although this form of regulation was first described nearly two decades ago, it remains poorly understood at a mechanistic level. The prototype for a transcription factor controlled by posttranslational modification is E. coli Ada protein, a chemosensor that both repairs methylation damage in DNA and coordinates the resistance response to genotoxic methylating agents. Ada repairs methyl phosphotriester lesions in DNA by transferring the aberrant methyl group to one of its own cysteine residues; this site-specific methylation enhances tremendously the DNA binding activity of the protein, thereby enabling it to activate a methylation-resistance regulon. Here, we report solution and X-ray structures of the Cys-methylated chemosensor domain of Ada bound to DNA. The structures reveal that both phosphotriester repair and methylation-dependent transcriptional activation function through a zinc- and methylation-dependent electrostatic switch.

About this Structure

1ZGW is a Single protein structure of sequence from Escherichia coli with as ligand. Full crystallographic information is available from OCA.

Reference

A methylation-dependent electrostatic switch controls DNA repair and transcriptional activation by E. coli ada., He C, Hus JC, Sun LJ, Zhou P, Norman DP, Dotsch V, Wei H, Gross JD, Lane WS, Wagner G, Verdine GL, Mol Cell. 2005 Oct 7;20(1):117-29. PMID:16209950

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