2ssp: Difference between revisions
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New page: left|200px<br /> <applet load="2ssp" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ssp, resolution 2.25Å" /> '''LEUCINE-272-ALANINE... |
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[[Image:2ssp.gif|left|200px]]<br /> | [[Image:2ssp.gif|left|200px]]<br /><applet load="2ssp" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="2ssp" size=" | |||
caption="2ssp, resolution 2.25Å" /> | caption="2ssp, resolution 2.25Å" /> | ||
'''LEUCINE-272-ALANINE URACIL-DNA GLYCOSYLASE BOUND TO ABASIC SITE-CONTAINING DNA'''<br /> | '''LEUCINE-272-ALANINE URACIL-DNA GLYCOSYLASE BOUND TO ABASIC SITE-CONTAINING DNA'''<br /> | ||
==Overview== | ==Overview== | ||
Three high-resolution crystal structures of DNA complexes with wild-type | 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. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
2SSP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Uridine_nucleosidase Uridine nucleosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.3 3.2.2.3] Full crystallographic information is available from [http:// | 2SSP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Uridine_nucleosidase Uridine nucleosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.3 3.2.2.3] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2SSP OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Uridine nucleosidase]] | [[Category: Uridine nucleosidase]] | ||
[[Category: Bharati, S.]] | [[Category: Bharati, S.]] | ||
[[Category: Krokan, H | [[Category: Krokan, H E.]] | ||
[[Category: Mol, C | [[Category: Mol, C D.]] | ||
[[Category: Parikh, S | [[Category: Parikh, S S.]] | ||
[[Category: Slupphaug, G.]] | [[Category: Slupphaug, G.]] | ||
[[Category: Tainer, J | [[Category: Tainer, J A.]] | ||
[[Category: abasic site]] | [[Category: abasic site]] | ||
[[Category: dna]] | [[Category: dna]] | ||
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[[Category: uracil]] | [[Category: uracil]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:49:27 2008'' | ||
