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| {{STRUCTURE_2ssp| PDB=2ssp | SCENE= }} | | {{STRUCTURE_2ssp| PDB=2ssp | SCENE= }} |
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| '''LEUCINE-272-ALANINE URACIL-DNA GLYCOSYLASE BOUND TO ABASIC SITE-CONTAINING DNA'''
| | ===LEUCINE-272-ALANINE URACIL-DNA GLYCOSYLASE BOUND TO ABASIC SITE-CONTAINING DNA=== |
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| ==Overview==
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| Three high-resolution crystal structures of DNA complexes with wild-type and mutant human uracil-DNA glycosylase (UDG), coupled kinetic characterizations and comparisons with the refined unbound UDG structure help resolve fundamental issues in the initiation of DNA base excision repair (BER): damage detection, nucleotide flipping versus extrahelical nucleotide capture, avoidance of apurinic/apyrimidinic (AP) site toxicity and coupling of damage-specific and damage-general BER steps. Structural and kinetic results suggest that UDG binds, kinks and compresses the DNA backbone with a 'Ser-Pro pinch' and scans the minor groove for damage. Concerted shifts in UDG simultaneously form the catalytically competent active site and induce further compression and kinking of the double-stranded DNA backbone only at uracil and AP sites, where these nucleotides can flip at the phosphate-sugar junction into a complementary specificity pocket. Unexpectedly, UDG binds to AP sites more tightly and more rapidly than to uracil-containing DNA, and thus may protect cells sterically from AP site toxicity. Furthermore, AP-endonuclease, which catalyzes the first damage-general step of BER, enhances UDG activity, most likely by inducing UDG release via shared minor groove contacts and flipped AP site binding. Thus, AP site binding may couple damage-specific and damage-general steps of BER without requiring direct protein-protein interactions.
| | The line below this paragraph, {{ABSTRACT_PUBMED_9724657}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 9724657 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_9724657}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Protein/dna]] | | [[Category: Protein/dna]] |
| [[Category: Uracil]] | | [[Category: Uracil]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 17:21:29 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 10:06:17 2008'' |