2ssp
From Proteopedia
(New page: 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" |
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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'' |
Revision as of 16:49, 21 February 2008
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LEUCINE-272-ALANINE URACIL-DNA GLYCOSYLASE BOUND TO ABASIC SITE-CONTAINING DNA
Contents |
Overview
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
Known diseases associated with this structure: Immunodeficiency with hyper IgM, type 4 OMIM:[191525]
About this Structure
2SSP is a Single protein structure of sequence from Homo sapiens. Active as Uridine nucleosidase, with EC number 3.2.2.3 Full crystallographic information is available from OCA.
Reference
Base excision repair initiation revealed by crystal structures and binding kinetics of human uracil-DNA glycosylase with DNA., Parikh SS, Mol CD, Slupphaug G, Bharati S, Krokan HE, Tainer JA, EMBO J. 1998 Sep 1;17(17):5214-26. PMID:9724657
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