1t39

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[[Image:1t39.gif|left|200px]]
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{{STRUCTURE_1t39| PDB=1t39 | SCENE= }}
{{STRUCTURE_1t39| PDB=1t39 | SCENE= }}
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'''HUMAN O6-ALKYLGUANINE-DNA ALKYLTRANSFERASE COVALENTLY CROSSLINKED TO DNA'''
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===HUMAN O6-ALKYLGUANINE-DNA ALKYLTRANSFERASE COVALENTLY CROSSLINKED TO DNA===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 15221026 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15221026}}
==About this Structure==
==About this Structure==
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[[Category: Helix-turn-helix]]
[[Category: Helix-turn-helix]]
[[Category: Methyltransferase]]
[[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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Revision as of 21:01, 28 July 2008

Image:1t39.png

Template:STRUCTURE 1t39

HUMAN O6-ALKYLGUANINE-DNA ALKYLTRANSFERASE COVALENTLY CROSSLINKED TO DNA

Template:ABSTRACT PUBMED 15221026

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

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