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| | ==WILD-TYPE URACIL-DNA GLYCOSYLASE BOUND TO URACIL-CONTAINING DNA== | | ==WILD-TYPE URACIL-DNA GLYCOSYLASE BOUND TO URACIL-CONTAINING DNA== |
| - | <StructureSection load='1ssp' size='340' side='right' caption='[[1ssp]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='1ssp' size='340' side='right'caption='[[1ssp]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1ssp]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SSP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1SSP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1ssp]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SSP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SSP FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=URA:URACIL'>URA</scene>, <scene name='pdbligand=ORP:2-DEOXY-5-PHOSPHONO-RIBOSE'>ORP</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ORP:2-DEOXY-5-PHOSPHONO-RIBOSE'>ORP</scene>, <scene name='pdbligand=URA:URACIL'>URA</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ssp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ssp OCA], [http://pdbe.org/1ssp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ssp RCSB], [http://www.ebi.ac.uk/pdbsum/1ssp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1ssp ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ssp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ssp OCA], [https://pdbe.org/1ssp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ssp RCSB], [https://www.ebi.ac.uk/pdbsum/1ssp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ssp ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/UNG_HUMAN UNG_HUMAN]] Defects in UNG are a cause of immunodeficiency with hyper-IgM type 5 (HIGM5) [MIM:[http://omim.org/entry/608106 608106]]. A rare immunodeficiency syndrome characterized by normal or elevated serum IgM levels with absence of IgG, IgA, and IgE. It results in a profound susceptibility to bacterial infections.<ref>PMID:12958596</ref> <ref>PMID:15967827</ref> | + | [https://www.uniprot.org/uniprot/UNG_HUMAN UNG_HUMAN] Defects in UNG are a cause of immunodeficiency with hyper-IgM type 5 (HIGM5) [MIM:[https://omim.org/entry/608106 608106]. A rare immunodeficiency syndrome characterized by normal or elevated serum IgM levels with absence of IgG, IgA, and IgE. It results in a profound susceptibility to bacterial infections.<ref>PMID:12958596</ref> <ref>PMID:15967827</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/UNG_HUMAN UNG_HUMAN]] Excises uracil residues from the DNA which can arise as a result of misincorporation of dUMP residues by DNA polymerase or due to deamination of cytosine. | + | [https://www.uniprot.org/uniprot/UNG_HUMAN UNG_HUMAN] Excises uracil residues from the DNA which can arise as a result of misincorporation of dUMP residues by DNA polymerase or due to deamination of cytosine. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[DNA glycosylase|DNA glycosylase]] | + | *[[DNA glycosylase 3D structures|DNA glycosylase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Uridine nucleosidase]] | + | [[Category: Large Structures]] |
| - | [[Category: Bharati, S]] | + | [[Category: Bharati S]] |
| - | [[Category: Krokan, H E]] | + | [[Category: Krokan HE]] |
| - | [[Category: Mol, C D]] | + | [[Category: Mol CD]] |
| - | [[Category: Parikh, S S]] | + | [[Category: Parikh SS]] |
| - | [[Category: Slupphaug, G]] | + | [[Category: Slupphaug G]] |
| - | [[Category: Tainer, J A]] | + | [[Category: Tainer JA]] |
| - | [[Category: Dna]]
| + | |
| - | [[Category: Dna base excision repair]]
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| - | [[Category: Dna glycosylase]]
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| - | [[Category: Hydrolase-dna complex]]
| + | |
| - | [[Category: Protein/dna]]
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| - | [[Category: Uracil]]
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| Structural highlights
Disease
UNG_HUMAN Defects in UNG are a cause of immunodeficiency with hyper-IgM type 5 (HIGM5) [MIM:608106. A rare immunodeficiency syndrome characterized by normal or elevated serum IgM levels with absence of IgG, IgA, and IgE. It results in a profound susceptibility to bacterial infections.[1] [2]
Function
UNG_HUMAN Excises uracil residues from the DNA which can arise as a result of misincorporation of dUMP residues by DNA polymerase or due to deamination of cytosine.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Imai K, Slupphaug G, Lee WI, Revy P, Nonoyama S, Catalan N, Yel L, Forveille M, Kavli B, Krokan HE, Ochs HD, Fischer A, Durandy A. Human uracil-DNA glycosylase deficiency associated with profoundly impaired immunoglobulin class-switch recombination. Nat Immunol. 2003 Oct;4(10):1023-8. Epub 2003 Sep 7. PMID:12958596 doi:http://dx.doi.org/10.1038/ni974
- ↑ Kavli B, Andersen S, Otterlei M, Liabakk NB, Imai K, Fischer A, Durandy A, Krokan HE, Slupphaug G. B cells from hyper-IgM patients carrying UNG mutations lack ability to remove uracil from ssDNA and have elevated genomic uracil. J Exp Med. 2005 Jun 20;201(12):2011-21. PMID:15967827 doi:10.1084/jem.20050042
- ↑ Parikh SS, Mol CD, Slupphaug G, Bharati S, Krokan HE, Tainer JA. Base excision repair initiation revealed by crystal structures and binding kinetics of human uracil-DNA glycosylase with DNA. EMBO J. 1998 Sep 1;17(17):5214-26. PMID:9724657 doi:10.1093/emboj/17.17.5214
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