1p7m
From Proteopedia
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[[Image:1p7m.gif|left|200px]] | [[Image:1p7m.gif|left|200px]] | ||
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'''SOLUTION STRUCTURE AND BASE PERTURBATION STUDIES REVEAL A NOVEL MODE OF ALKYLATED BASE RECOGNITION BY 3-METHYLADENINE DNA GLYCOSYLASE I''' | '''SOLUTION STRUCTURE AND BASE PERTURBATION STUDIES REVEAL A NOVEL MODE OF ALKYLATED BASE RECOGNITION BY 3-METHYLADENINE DNA GLYCOSYLASE I''' | ||
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[[Category: Stivers, J T.]] | [[Category: Stivers, J T.]] | ||
[[Category: 3-methyladenine tag complex nmr]] | [[Category: 3-methyladenine tag complex nmr]] | ||
- | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 04:47:10 2008'' | |
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Revision as of 01:47, 3 May 2008
SOLUTION STRUCTURE AND BASE PERTURBATION STUDIES REVEAL A NOVEL MODE OF ALKYLATED BASE RECOGNITION BY 3-METHYLADENINE DNA GLYCOSYLASE I
Overview
The specific recognition mechanisms of DNA repair glycosylases that remove cationic alkylpurine bases in DNA are not well understood partly due to the absence of structures of these enzymes with their cognate bases. Here we report the solution structure of 3-methyladenine DNA glycosylase I (TAG) in complex with its 3-methyladenine (3-MeA) cognate base, and we have used chemical perturbation of the base in combination with mutagenesis of the enzyme to evaluate the role of hydrogen bonding and pi-cation interactions in alkylated base recognition by this DNA repair enzyme. We find that TAG uses hydrogen bonding with heteroatoms on the base, van der Waals interactions with the 3-Me group, and conventional pi-pi stacking with a conserved Trp side chain to selectively bind neutral 3-MeA over the cationic form of the base. Discrimination against binding of the normal base adenine is derived from direct sensing of the 3-methyl group, leading to an induced-fit conformational change that engulfs the base in a box defined by five aromatic side chains. These findings indicate that base specific recognition by TAG does not involve strong pi-cation interactions, and suggest a novel mechanism for alkylated base recognition and removal.
About this Structure
1P7M is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
Reference
Solution structure and base perturbation studies reveal a novel mode of alkylated base recognition by 3-methyladenine DNA glycosylase I., Cao C, Kwon K, Jiang YL, Drohat AC, Stivers JT, J Biol Chem. 2003 Nov 28;278(48):48012-20. Epub 2003 Sep 16. PMID:13129925 Page seeded by OCA on Sat May 3 04:47:10 2008