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| | <StructureSection load='5cl3' size='340' side='right'caption='[[5cl3]], [[Resolution|resolution]] 1.97Å' scene=''> | | <StructureSection load='5cl3' size='340' side='right'caption='[[5cl3]], [[Resolution|resolution]] 1.97Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5cl3]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_14579 Atcc 14579]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CL3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CL3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5cl3]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_cereus Bacillus cereus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CL3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CL3 FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DZM:3-DEAZA-3-METHYLADENINE'>DZM</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DZM:3-DEAZA-3-METHYLADENINE'>DZM</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5cl4|5cl4]], [[5cl5|5cl5]], [[5cl6|5cl6]], [[5cl7|5cl7]], [[5cl8|5cl8]], [[5cl9|5cl9]], [[5cla|5cla]], [[5clb|5clb]], [[5clc|5clc]], [[5cld|5cld]], [[5cle|5cle]]</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=5cl3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cl3 OCA], [https://pdbe.org/5cl3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5cl3 RCSB], [https://www.ebi.ac.uk/pdbsum/5cl3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5cl3 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IKE_03968 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1396 ATCC 14579])</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=5cl3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cl3 OCA], [http://pdbe.org/5cl3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cl3 RCSB], [http://www.ebi.ac.uk/pdbsum/5cl3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5cl3 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q816E8_BACCR Q816E8_BACCR] |
| | <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 5cl3" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5cl3" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[DNA glycosylase 3D structures|DNA glycosylase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 14579]] | + | [[Category: Bacillus cereus]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Eichman, B F]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Mullins, E A]] | + | [[Category: Eichman BF]] |
| - | [[Category: Dna glycosylase]] | + | [[Category: Mullins EA]] |
| - | [[Category: Heat-like repeat]]
| + | |
| - | [[Category: Hydrolase-dna complex]]
| + | |
| - | [[Category: Protein-dna complex]]
| + | |
| Structural highlights
Function
Q816E8_BACCR
Publication Abstract from PubMed
Threats to genomic integrity arising from DNA damage are mitigated by DNA glycosylases, which initiate the base excision repair pathway by locating and excising aberrant nucleobases. How these enzymes find small modifications within the genome is a current area of intensive research. A hallmark of these and other DNA repair enzymes is their use of base flipping to sequester modified nucleotides from the DNA helix and into an active site pocket. Consequently, base flipping is generally regarded as an essential aspect of lesion recognition and a necessary precursor to base excision. Here we present the first, to our knowledge, DNA glycosylase mechanism that does not require base flipping for either binding or catalysis. Using the DNA glycosylase AlkD from Bacillus cereus, we crystallographically monitored excision of an alkylpurine substrate as a function of time, and reconstructed the steps along the reaction coordinate through structures representing substrate, intermediate and product complexes. Instead of directly interacting with the damaged nucleobase, AlkD recognizes aberrant base pairs through interactions with the phosphoribose backbone, while the lesion remains stacked in the DNA duplex. Quantum mechanical calculations revealed that these contacts include catalytic charge-dipole and CH-pi interactions that preferentially stabilize the transition state. We show in vitro and in vivo how this unique means of recognition and catalysis enables AlkD to repair large adducts formed by yatakemycin, a member of the duocarmycin family of antimicrobial natural products exploited in bacterial warfare and chemotherapeutic trials. Bulky adducts of this or any type are not excised by DNA glycosylases that use a traditional base-flipping mechanism. Hence, these findings represent a new model for DNA repair and provide insights into catalysis of base excision.
The DNA glycosylase AlkD uses a non-base-flipping mechanism to excise bulky lesions.,Mullins EA, Shi R, Parsons ZD, Yuen PK, David SS, Igarashi Y, Eichman BF Nature. 2015 Nov 12;527(7577):254-8. doi: 10.1038/nature15728. Epub 2015 Oct 28. PMID:26524531[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Mullins EA, Shi R, Parsons ZD, Yuen PK, David SS, Igarashi Y, Eichman BF. The DNA glycosylase AlkD uses a non-base-flipping mechanism to excise bulky lesions. Nature. 2015 Nov 12;527(7577):254-8. doi: 10.1038/nature15728. Epub 2015 Oct 28. PMID:26524531 doi:http://dx.doi.org/10.1038/nature15728
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