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|a Setser, Jeremy W.
|e author
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|a Massachusetts Institute of Technology. Center for Environmental Health Sciences
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|a Massachusetts Institute of Technology. Department of Biological Engineering
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|a Massachusetts Institute of Technology. Department of Chemistry
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|a Koch Institute for Integrative Cancer Research at MIT
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|a Drennan, Catherine L.
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|a Drennan, Catherine L.
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|a Lingaraju, Gondichatnahalli M.
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|a Davis, C. Ainsley
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|a Samson, Leona D.
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|a Drennan, Catherine L
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|a Searching for DNA Lesions: Structural Evidence for Lower- and Higher-Affinity DNA Binding Conformations of Human Alkyladenine DNA Glycosylase
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|b American Chemical Society,
|c 2012-10-04T13:40:24Z.
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|z Get fulltext
|u http://hdl.handle.net/1721.1/73589
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|a To efficiently repair DNA, human alkyladenine DNA glycosylase (AAG) must search the million-fold excess of unmodified DNA bases to find a handful of DNA lesions. Such a search can be facilitated by the ability of glycosylases, like AAG, to interact with DNA using two affinities: a lower-affinity interaction in a searching process and a higher-affinity interaction for catalytic repair. Here, we present crystal structures of AAG trapped in two DNA-bound states. The lower-affinity depiction allows us to investigate, for the first time, the conformation of this protein in the absence of a tightly bound DNA adduct. We find that active site residues of AAG involved in binding lesion bases are in a disordered state. Furthermore, two loops that contribute significantly to the positive electrostatic surface of AAG are disordered. Additionally, a higher-affinity state of AAG captured here provides a fortuitous snapshot of how this enzyme interacts with a DNA adduct that resembles a one-base loop.
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|a National Institutes of Health (U.S.) (grant no. P30-ES002109)
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|a National Institutes of Health (U.S.) (grant no. GM65337)
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|a National Institutes of Health (U.S.) (grant no. GM65337-03S2)
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|a National Institutes of Health (U.S.) (grant no. CA055042)
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|a National Institutes of Health (U.S.) (grant no. CA092584)
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|a Repligen Corporation (KIICR Graduate Fellowship)
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|a en_US
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|a Article
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|t Biochemistry
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