1mwj
From Proteopedia
(New page: 200px<br /><applet load="1mwj" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mwj, resolution 2.85Å" /> '''Crystal Structure of...) |
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| - | [[Image:1mwj.gif|left|200px]]<br /><applet load="1mwj" size=" | + | [[Image:1mwj.gif|left|200px]]<br /><applet load="1mwj" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1mwj, resolution 2.85Å" /> | caption="1mwj, resolution 2.85Å" /> | ||
'''Crystal Structure of a MUG-DNA pseudo substrate complex'''<br /> | '''Crystal Structure of a MUG-DNA pseudo substrate complex'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The bacterial mismatch-specific uracil-DNA glycosylase (MUG) and | + | The bacterial mismatch-specific uracil-DNA glycosylase (MUG) and eukaryotic thymine-DNA glycosylase (TDG) enzymes form a homologous family of DNA glycosylases that initiate base-excision repair of G:U/T mismatches. Despite low sequence homology, the MUG/TDG enzymes are structurally related to the uracil-DNA glycosylase enzymes, but have a very different mechanism for substrate recognition. We have now determined the crystal structure of the Escherichia coli MUG enzyme complexed with an oligonucleotide containing a non-hydrolysable deoxyuridine analogue mismatched with guanine, providing the first structure of an intact substrate-nucleotide productively bound to a hydrolytic DNA glycosylase. The structure of this complex explains the preference for G:U over G:T mispairs, and reveals an essentially non-specific pyrimidine-binding pocket that allows MUG/TDG enzymes to excise the alkylated base, 3, N(4)-ethenocytosine. Together with structures for the free enzyme and for an abasic-DNA product complex, the MUG-substrate analogue complex reveals the conformational changes accompanying the catalytic cycle of substrate binding, base excision and product release. |
==About this Structure== | ==About this Structure== | ||
| - | 1MWJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http:// | + | 1MWJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MWJ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Barrett, T | + | [[Category: Barrett, T E.]] |
[[Category: Brown, T.]] | [[Category: Brown, T.]] | ||
[[Category: Jiricny, J.]] | [[Category: Jiricny, J.]] | ||
| - | [[Category: Pearl, L | + | [[Category: Pearl, L H.]] |
[[Category: Savva, R.]] | [[Category: Savva, R.]] | ||
[[Category: Scharer, O.]] | [[Category: Scharer, O.]] | ||
| - | [[Category: Verdine, G | + | [[Category: Verdine, G L.]] |
[[Category: non-hydrolysable dna-complex]] | [[Category: non-hydrolysable dna-complex]] | ||
[[Category: rossmann fold]] | [[Category: rossmann fold]] | ||
[[Category: uracil recognition.]] | [[Category: uracil recognition.]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:59:46 2008'' |
Revision as of 11:59, 21 February 2008
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Crystal Structure of a MUG-DNA pseudo substrate complex
Overview
The bacterial mismatch-specific uracil-DNA glycosylase (MUG) and eukaryotic thymine-DNA glycosylase (TDG) enzymes form a homologous family of DNA glycosylases that initiate base-excision repair of G:U/T mismatches. Despite low sequence homology, the MUG/TDG enzymes are structurally related to the uracil-DNA glycosylase enzymes, but have a very different mechanism for substrate recognition. We have now determined the crystal structure of the Escherichia coli MUG enzyme complexed with an oligonucleotide containing a non-hydrolysable deoxyuridine analogue mismatched with guanine, providing the first structure of an intact substrate-nucleotide productively bound to a hydrolytic DNA glycosylase. The structure of this complex explains the preference for G:U over G:T mispairs, and reveals an essentially non-specific pyrimidine-binding pocket that allows MUG/TDG enzymes to excise the alkylated base, 3, N(4)-ethenocytosine. Together with structures for the free enzyme and for an abasic-DNA product complex, the MUG-substrate analogue complex reveals the conformational changes accompanying the catalytic cycle of substrate binding, base excision and product release.
About this Structure
1MWJ is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
Reference
Crystal structure of a thwarted mismatch glycosylase DNA repair complex., Barrett TE, Scharer OD, Savva R, Brown T, Jiricny J, Verdine GL, Pearl LH, EMBO J. 1999 Dec 1;18(23):6599-609. PMID:10581234
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