5cl6: Difference between revisions
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==Alkylpurine DNA glycosylase AlkD bound to DNA containing a 3-methyladenine analog or DNA containing an abasic site and a free nucleobase (33% substrate/67% product at 72 hours)== | ==Alkylpurine DNA glycosylase AlkD bound to DNA containing a 3-methyladenine analog or DNA containing an abasic site and a free nucleobase (33% substrate/67% product at 72 hours)== | ||
<StructureSection load='5cl6' size='340' side='right' caption='[[5cl6]], [[Resolution|resolution]] 1.54Å' scene=''> | <StructureSection load='5cl6' size='340' side='right'caption='[[5cl6]], [[Resolution|resolution]] 1.54Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5cl6]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CL6 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5cl6]] 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=5CL6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CL6 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.541Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=54K:7-METHYL-3H-IMIDAZO[4,5-C]PYRIDIN-4-AMINE'>54K</scene>, <scene name='pdbligand=DZM:3-DEAZA-3-METHYLADENINE'>DZM</scene>, <scene name='pdbligand=ORP:2-DEOXY-5-PHOSPHONO-RIBOSE'>ORP</scene></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=5cl6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cl6 OCA], [https://pdbe.org/5cl6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5cl6 RCSB], [https://www.ebi.ac.uk/pdbsum/5cl6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5cl6 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</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 5cl6" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5cl6" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[DNA glycosylase 3D structures|DNA glycosylase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Bacillus cereus]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Synthetic construct]] | ||
[[Category: | [[Category: Eichman BF]] | ||
[[Category: | [[Category: Mullins EA]] | ||
Latest revision as of 11:38, 27 September 2023
Alkylpurine DNA glycosylase AlkD bound to DNA containing a 3-methyladenine analog or DNA containing an abasic site and a free nucleobase (33% substrate/67% product at 72 hours)Alkylpurine DNA glycosylase AlkD bound to DNA containing a 3-methyladenine analog or DNA containing an abasic site and a free nucleobase (33% substrate/67% product at 72 hours)
Structural highlights
FunctionPublication Abstract from PubMedThreats 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 AlsoReferences
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