View source for 4uqm


==Crystal structure determination of uracil-DNA N-glycosylase (UNG) from Deinococcus radiodurans in complex with DNA - new insights into the role of the Leucine-loop for damage recognition and repair==
<StructureSection load='4uqm' size='340' side='right'caption='[[4uqm]], [[Resolution|resolution]] 1.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4uqm]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Deinococcus_radiodurans Deinococcus radiodurans] 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=4UQM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UQM FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.35&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AAB:2-DEOXY-RIBOFURANOSE-5-MONOPHOSPHATE'>AAB</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=4uqm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uqm OCA], [https://pdbe.org/4uqm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4uqm RCSB], [https://www.ebi.ac.uk/pdbsum/4uqm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4uqm ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/UNG_DEIRA UNG_DEIRA] 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 (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Uracil-DNA N-glycosylase (UNG) is a DNA-repair enzyme in the base-excision repair (BER) pathway which removes uracil from DNA. Here, the crystal structure of UNG from the extremophilic bacterium Deinococcus radiodurans (DrUNG) in complex with DNA is reported at a resolution of 1.35 A. Prior to the crystallization experiments, the affinity between DrUNG and different DNA oligonucleotides was tested by electrophoretic mobility shift assays (EMSAs). As a result of this analysis, two 16 nt double-stranded DNAs were chosen for the co-crystallization experiments, one of which (16 nt AU) resulted in well diffracting crystals. The DNA in the co-crystal structure contained an abasic site (substrate product) flipped into the active site of the enzyme, with no uracil in the active-site pocket. Despite the high resolution, it was not possible to fit all of the terminal nucleotides of the DNA complex into electron density owing to disorder caused by a lack of stabilizing interactions. However, the DNA which was in contact with the enzyme, close to the active site, was well ordered and allowed detailed analysis of the enzyme-DNA interaction. The complex revealed that the interaction between DrUNG and DNA is similar to that in the previously determined crystal structure of human UNG (hUNG) in complex with DNA [Slupphaug et al. (1996). Nature (London), 384, 87-92]. Substitutions in a (here defined) variable part of the leucine loop result in a shorter loop (eight residues instead of nine) in DrUNG compared with hUNG; regardless of this, it seems to fulfil its role and generate a stabilizing force with the minor groove upon flipping out of the damaged base into the active site. The structure also provides a rationale for the previously observed high catalytic efficiency of DrUNG caused by high substrate affinity by demonstrating an increased number of long-range electrostatic interactions between the enzyme and the DNA. Interestingly, specific interactions between residues in the N-terminus of a symmetry-related molecule and the complementary DNA strand facing away from the active site were also observed which seem to stabilize the enzyme-DNA complex. However, the significance of this observation remains to be investigated. The results provide new insights into the current knowledge about DNA damage recognition and repair by uracil-DNA glycosylases.

Structure determination of uracil-DNA N-glycosylase from Deinococcus radiodurans in complex with DNA.,Pedersen HL, Johnson KA, McVey CE, Leiros I, Moe E Acta Crystallogr D Biol Crystallogr. 2015 Oct;71(Pt 10):2137-49. doi:, 10.1107/S1399004715014157. Epub 2015 Sep 30. PMID:26457437<ref>PMID:26457437</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4uqm" style="background-color:#fffaf0;"></div>

==See Also==
*[[DNA glycosylase 3D structures|DNA glycosylase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Deinococcus radiodurans]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Johnson KA]]
[[Category: Leiros I]]
[[Category: McVey CE]]
[[Category: Moe E]]
[[Category: Pedersen HL]]