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| | ==Structure of E. coli Nfo(Endo IV)-H69A mutant bound to a cleaved DNA duplex containing a alphadA:T basepair== | | ==Structure of E. coli Nfo(Endo IV)-H69A mutant bound to a cleaved DNA duplex containing a alphadA:T basepair== |
| - | <StructureSection load='4k1g' size='340' side='right' caption='[[4k1g]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='4k1g' size='340' side='right'caption='[[4k1g]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4k1g]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4K1G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4K1G FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4k1g]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4K1G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4K1G FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2nqj|2nqj]], [[2nq9|2nq9]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">nfo, b2159, JW2146 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</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=4k1g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k1g OCA], [https://pdbe.org/4k1g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4k1g RCSB], [https://www.ebi.ac.uk/pdbsum/4k1g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4k1g ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Deoxyribonuclease_IV_(phage-T(4)-induced) Deoxyribonuclease IV (phage-T(4)-induced)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.21.2 3.1.21.2] </span></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=4k1g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k1g OCA], [http://pdbe.org/4k1g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4k1g RCSB], [http://www.ebi.ac.uk/pdbsum/4k1g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4k1g ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/END4_ECOLI END4_ECOLI]] Endonuclease IV plays a role in DNA repair. It cleaves phosphodiester bonds at apurinic or apyrimidinic sites (AP sites) to produce new 5'-ends that are base-free deoxyribose 5-phosphate residues. It preferentially attacks modified AP sites created by bleomycin and neocarzinostatin. | + | [https://www.uniprot.org/uniprot/END4_ECOLI END4_ECOLI] Endonuclease IV plays a role in DNA repair. It cleaves phosphodiester bonds at apurinic or apyrimidinic sites (AP sites) to produce new 5'-ends that are base-free deoxyribose 5-phosphate residues. It preferentially attacks modified AP sites created by bleomycin and neocarzinostatin. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4k1g" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4k1g" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Endonuclease 3D structures|Endonuclease 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ecoli]] | + | [[Category: Escherichia coli K-12]] |
| - | [[Category: Morera, S]] | + | [[Category: Large Structures]] |
| - | [[Category: Vigouroux, A]] | + | [[Category: Morera S]] |
| - | [[Category: Dna endonuclease iv]] | + | [[Category: Vigouroux A]] |
| - | [[Category: Hydrolase-dna complex]]
| + | |
| Structural highlights
Function
END4_ECOLI Endonuclease IV plays a role in DNA repair. It cleaves phosphodiester bonds at apurinic or apyrimidinic sites (AP sites) to produce new 5'-ends that are base-free deoxyribose 5-phosphate residues. It preferentially attacks modified AP sites created by bleomycin and neocarzinostatin.
Publication Abstract from PubMed
8,5'-cyclo-2'-deoxyadenosine (cdA) and 8,5'-cyclo-2'-deoxyguanosine generated in DNA by both endogenous oxidative stress and ionizing radiation are helix-distorting lesions and strong blocks for DNA replication and transcription. In duplex DNA, these lesions are repaired in the nucleotide excision repair (NER) pathway. However, lesions at DNA strand breaks are most likely poor substrates for NER. Here we report that the apurinic/apyrimidinic (AP) endonucleases--Escherichia coli Xth and human APE1--can remove 5'S cdA (S-cdA) at 3' termini of duplex DNA. In contrast, E. coli Nfo and yeast Apn1 are unable to carry out this reaction. None of these enzymes can remove S-cdA adduct located at 1 or more nt away from the 3' end. To understand the structural basis of 3' repair activity, we determined a high-resolution crystal structure of E. coli Nfo-H69A mutant bound to a duplex DNA containing an alpha-anomeric 2'-deoxyadenosine:T base pair. Surprisingly, the structure reveals a bound nucleotide incision repair (NIR) product with an abortive 3'-terminal dC close to the scissile position in the enzyme active site, providing insight into the mechanism for Nfo-catalyzed 3'-->5' exonuclease function and its inhibition by 3'-terminal S-cdA residue. This structure was used as a template to model 3'-terminal residues in the APE1 active site and to explain biochemical data on APE1-catalyzed 3' repair activities. We propose that Xth and APE1 may act as a complementary repair pathway to NER to remove S-cdA adducts from 3' DNA termini in E. coli and human cells, respectively.
Insight into mechanisms of 3'-5' exonuclease activity and removal of bulky 8,5'-cyclopurine adducts by apurinic/apyrimidinic endonucleases.,Mazouzi A, Vigouroux A, Aikeshev B, Brooks PJ, Saparbaev MK, Morera S, Ishchenko AA Proc Natl Acad Sci U S A. 2013 Aug 13;110(33):E3071-80. doi:, 10.1073/pnas.1305281110. Epub 2013 Jul 29. PMID:23898172[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Mazouzi A, Vigouroux A, Aikeshev B, Brooks PJ, Saparbaev MK, Morera S, Ishchenko AA. Insight into mechanisms of 3'-5' exonuclease activity and removal of bulky 8,5'-cyclopurine adducts by apurinic/apyrimidinic endonucleases. Proc Natl Acad Sci U S A. 2013 Aug 13;110(33):E3071-80. doi:, 10.1073/pnas.1305281110. Epub 2013 Jul 29. PMID:23898172 doi:http://dx.doi.org/10.1073/pnas.1305281110
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