1t39

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[[Image:1t39.gif|left|200px]]
[[Image:1t39.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 1t39 |SIZE=350|CAPTION= <scene name='initialview01'>1t39</scene>, resolution 3.30&Aring;
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The line below this paragraph, containing "STRUCTURE_1t39", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=DA:2&#39;-DEOXYADENOSINE-5&#39;-MONOPHOSPHATE'>DA</scene>, <scene name='pdbligand=DC:2&#39;-DEOXYCYTIDINE-5&#39;-MONOPHOSPHATE'>DC</scene>, <scene name='pdbligand=DG:2&#39;-DEOXYGUANOSINE-5&#39;-MONOPHOSPHATE'>DG</scene>, <scene name='pdbligand=DT:THYMIDINE-5&#39;-MONOPHOSPHATE'>DT</scene>, <scene name='pdbligand=E1X:PHOSPHORIC+ACID+MONO-[5-(1-ETHYL-2,6-DIOXO-1,2,3,6-TETRAHYDRO-PURIN-9-YL)-3-HYDROXY-TETRAHYDRO-FURAN-2-YLMETHYL]ESTER'>E1X</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[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] </span>
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or leave the SCENE parameter empty for the default display.
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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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|DOMAIN=
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{{STRUCTURE_1t39| PDB=1t39 | SCENE= }}
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|RELATEDENTRY=[[1eh6|1EH6]], [[1eh7|1EH7]], [[1eh8|1EH8]], [[1t38|1T38]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1t39 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t39 OCA], [http://www.ebi.ac.uk/pdbsum/1t39 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1t39 RCSB]</span>
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}}
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'''HUMAN O6-ALKYLGUANINE-DNA ALKYLTRANSFERASE COVALENTLY CROSSLINKED TO DNA'''
'''HUMAN O6-ALKYLGUANINE-DNA ALKYLTRANSFERASE COVALENTLY CROSSLINKED TO DNA'''
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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]
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]]
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[[Category: Methylated-DNA--[protein]-cysteine S-methyltransferase]]
 
[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Clarke, N D.]]
[[Category: Clarke, N D.]]
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[[Category: Tainer, J A.]]
[[Category: Tainer, J A.]]
[[Category: Woo, T T.]]
[[Category: Woo, T T.]]
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[[Category: alkyltransferase]]
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[[Category: Alkyltransferase]]
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[[Category: dna repair]]
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[[Category: Dna repair]]
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[[Category: helix-turn-helix]]
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[[Category: Helix-turn-helix]]
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[[Category: methyltransferase]]
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[[Category: Methyltransferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 09:27:49 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:50:36 2008''
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Revision as of 06:27, 3 May 2008

Image:1t39.gif

Template:STRUCTURE 1t39

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 Page seeded by OCA on Sat May 3 09:27:49 2008

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