1t39

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[[Image:1t39.gif|left|200px]]<br /><applet load="1t39" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1t39.gif|left|200px]]
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caption="1t39, resolution 3.30&Aring;" />
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'''HUMAN O6-ALKYLGUANINE-DNA ALKYLTRANSFERASE COVALENTLY CROSSLINKED TO DNA'''<br />
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{{Structure
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|PDB= 1t39 |SIZE=350|CAPTION= <scene name='initialview01'>1t39</scene>, resolution 3.30&Aring;
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|SITE=
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|LIGAND=
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|ACTIVITY= [http://en.wikipedia.org/wiki/Methylated-DNA--[protein]-cysteine_S-methyltransferase Methylated-DNA--[protein]-cysteine S-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.63 2.1.1.63]
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|GENE= MGMT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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}}
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'''HUMAN O6-ALKYLGUANINE-DNA ALKYLTRANSFERASE COVALENTLY CROSSLINKED TO DNA'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1T39 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Methylated-DNA--[protein]-cysteine_S-methyltransferase Methylated-DNA--[protein]-cysteine S-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.63 2.1.1.63] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T39 OCA].
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1T39 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T39 OCA].
==Reference==
==Reference==
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DNA binding and nucleotide flipping by the human DNA repair protein AGT., Daniels DS, Woo TT, Luu KX, Noll DM, Clarke ND, Pegg AE, Tainer JA, Nat Struct Mol Biol. 2004 Aug;11(8):714-20. Epub 2004 Jun 27. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15221026 15221026]
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DNA binding and nucleotide flipping by the human DNA repair protein AGT., Daniels DS, Woo TT, Luu KX, Noll DM, Clarke ND, Pegg AE, Tainer JA, Nat Struct Mol Biol. 2004 Aug;11(8):714-20. Epub 2004 Jun 27. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15221026 15221026]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Methylated-DNA--[protein]-cysteine S-methyltransferase]]
[[Category: Methylated-DNA--[protein]-cysteine S-methyltransferase]]
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[[Category: methyltransferase]]
[[Category: methyltransferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:09:22 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:13:09 2008''

Revision as of 12:13, 20 March 2008


PDB ID 1t39

Drag the structure with the mouse to rotate
, resolution 3.30Å
Gene: MGMT (Homo sapiens)
Activity: [protein-cysteine_S-methyltransferase Methylated-DNA--[protein]-cysteine S-methyltransferase], with EC number 2.1.1.63
Coordinates: save as pdb, mmCIF, xml



HUMAN O6-ALKYLGUANINE-DNA ALKYLTRANSFERASE COVALENTLY CROSSLINKED TO DNA


Overview

O(6)-alkylguanine-DNA alkyltransferase (AGT), or O(6)-methylguanine-DNA methyltransferase (MGMT), prevents mutations and apoptosis resulting from alkylation damage to guanines. AGT irreversibly transfers the alkyl lesion to an active site cysteine in a stoichiometric, direct damage reversal pathway. AGT expression therefore elicits tumor resistance to alkylating chemotherapies, and AGT inhibitors are in clinical trials. We report here structures of human AGT in complex with double-stranded DNA containing the biological substrate O(6)-methylguanine or crosslinked to the mechanistic inhibitor N(1),O(6)-ethanoxanthosine. The prototypical DNA major groove-binding helix-turn-helix (HTH) motif mediates unprecedented minor groove DNA binding. This binding architecture has advantages for DNA repair and nucleotide flipping, and provides a paradigm for HTH interactions in sequence-independent DNA-binding proteins like RecQ and BRCA2. Structural and biochemical results further support an unpredicted role for Tyr114 in nucleotide flipping through phosphate rotation and an efficient kinetic mechanism for locating alkylated bases.

About this Structure

1T39 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

DNA binding and nucleotide flipping by the human DNA repair protein AGT., Daniels DS, Woo TT, Luu KX, Noll DM, Clarke ND, Pegg AE, Tainer JA, Nat Struct Mol Biol. 2004 Aug;11(8):714-20. Epub 2004 Jun 27. PMID:15221026[[Category: Methylated-DNA--[protein]-cysteine S-methyltransferase]]

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