View source for 4yoq


==Crystal Structure of MutY bound to its anti-substrate==
<StructureSection load='4yoq' size='340' side='right'caption='[[4yoq]], [[Resolution|resolution]] 2.21&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4yoq]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Geobacillus_stearothermophilus Geobacillus stearothermophilus] 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=4YOQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YOQ 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]] 2.21&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8OG:8-OXO-2-DEOXY-GUANOSINE-5-MONOPHOSPHATE'>8OG</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=4yoq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yoq OCA], [https://pdbe.org/4yoq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yoq RCSB], [https://www.ebi.ac.uk/pdbsum/4yoq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yoq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MUTY_GEOSE MUTY_GEOSE] Base excision repair (BER) glycosylase that initiates repair of A:oxoG to C:G by removing the inappropriately paired adenine base from the DNA backbone, generating an abasic site product (PubMed:25995449) (PubMed:14961129). 8-oxoguanine (oxoG) is a genotoxic DNA lesion resulting from oxidation of guanine; this residue is misread by replicative DNA polymerases, that insert adenine instead of cytosine opposite the oxidized damaged base. Shows a powerful dicrimination of A versus C, since it does not cleave cytosine in oxoG:C pairs (PubMed:25995449). May also be able to remove adenine from A:G mispairs, although this activity may not be physiologically relevant (PubMed:14961129).<ref>PMID:25995449</ref> <ref>PMID:14961129</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The highly mutagenic A:oxoG base-pair in DNA most frequently arises by aberrant replication of the primary oxidative lesion C:oxoG. This lesion is particularly insidious, because neither of its constituent nucleobases faithfully transmit genetic information from the original C:G base-pair. Repair of A:oxoG is initiated by adenine DNA glycosylase which catalyzes hydrolytic cleavage of the aberrant A nucleobase from the DNA backbone. These enzymes, MutY in bacteria and hMYH in humans, scrupulously avoid processing of C:oxoG, because cleavage of the C residue in C:oxoG would actually promote mutagenic conversion to A:oxoG. Here we analyze the structural basis for rejection of C:oxoG by MutY, using a synthetic crystallography approach to capture the enzyme in the process of inspecting the C:oxoG anti-substrate, with which it ordinarily binds only fleetingly. We find that MutY uses two distinct strategies to avoid presentation of C to the enzyme active site. Firstly, MutY possesses an exo-site that serves as a decoy for C, and secondly, repulsive forces with a key active site residue prevent stable insertion of C into the nucleobase-recognition pocket within the enzyme active site.

Structural Basis for Avoidance of Promutagenic DNA Repair by MutY Adenine DNA Glycosylase.,Wang L, Lee SJ, Verdine G J Biol Chem. 2015 May 20. pii: jbc.M115.657866. PMID:25995449<ref>PMID:25995449</ref>

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

==See Also==
*[[DNA glycosylase 3D structures|DNA glycosylase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Geobacillus stearothermophilus]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Lee S]]
[[Category: Verdine GL]]
[[Category: Wang L]]