View source for 5uuj


==Streptomyces sahachiroi DNA glycosylase AlkZ==
<StructureSection load='5uuj' size='340' side='right'caption='[[5uuj]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5uuj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Streg Streg]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UUJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UUJ FirstGlance]. <br>
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5uuf|5uuf]], [[5uug|5uug]], [[5uuh|5uuh]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">azi36 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=285525 STREG])</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=5uuj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uuj OCA], [http://pdbe.org/5uuj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uuj RCSB], [http://www.ebi.ac.uk/pdbsum/5uuj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uuj ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
DNA glycosylases are important editing enzymes that protect genomic stability by excising chemically modified nucleobases that alter normal DNA metabolism. These enzymes have been known only to initiate base excision repair of small adducts by extrusion from the DNA helix. However, recent reports have described both vertebrate and microbial DNA glycosylases capable of unhooking highly toxic interstrand cross-links (ICLs) and bulky minor groove adducts normally recognized by Fanconi anemia and nucleotide excision repair machinery, although the mechanisms of these activities are unknown. Here we report the crystal structure of Streptomyces sahachiroi AlkZ (previously Orf1), a bacterial DNA glycosylase that protects its host by excising ICLs derived from azinomycin B (AZB), a potent antimicrobial and antitumor genotoxin. AlkZ adopts a unique fold in which three tandem winged helix-turn-helix motifs scaffold a positively charged concave surface perfectly shaped for duplex DNA. Through mutational analysis, we identified two glutamine residues and a beta-hairpin within this putative DNA-binding cleft that are essential for catalytic activity. Additionally, we present a molecular docking model for how this active site can unhook either or both sides of an AZB ICL, providing a basis for understanding the mechanisms of base excision repair of ICLs. Given the prevalence of this protein fold in pathogenic bacteria, this work also lays the foundation for an emerging role of DNA repair in bacteria-host pathogenesis.

Structure of a DNA glycosylase that unhooks interstrand cross-links.,Mullins EA, Warren GM, Bradley NP, Eichman BF Proc Natl Acad Sci U S A. 2017 Apr 25;114(17):4400-4405. doi:, 10.1073/pnas.1703066114. Epub 2017 Apr 10. PMID:28396405<ref>PMID:28396405</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5uuj" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streg]]
[[Category: Eichman, B F]]
[[Category: Mullins, E A]]
[[Category: Alkylpurine]]
[[Category: Azinomycin b]]
[[Category: Dna repair]]
[[Category: Hydrolase]]
[[Category: Interstrand crosslink]]