View source for 4jgc


==Human TDG N140A mutant IN A COMPLEX WITH 5-carboxylcytosine (5caC)==
<StructureSection load='4jgc' size='340' side='right'caption='[[4jgc]], [[Resolution|resolution]] 2.58&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4jgc]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JGC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JGC 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]] 2.582&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1RT:4-AMINO-2-OXO-1,2-DIHYDROPYRIMIDINE-5-CARBOXYLIC+ACID'>1RT</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=4jgc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jgc OCA], [https://pdbe.org/4jgc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jgc RCSB], [https://www.ebi.ac.uk/pdbsum/4jgc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jgc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TDG_HUMAN TDG_HUMAN] In the DNA of higher eukaryotes, hydrolytic deamination of 5-methylcytosine to thymine leads to the formation of G/T mismatches. This enzyme corrects G/T mispairs to G/C pairs. It is capable of hydrolyzing the carbon-nitrogen bond between the sugar-phosphate backbone of the DNA and a mispaired thymine. In addition to the G/T, it can remove thymine also from C/T and T/T mispairs in the order G/T >> C/T > T/T. It has no detectable activity on apyrimidinic sites and does not catalyze the removal of thymine from A/T pairs or from single-stranded DNA. It can also remove uracil and 5-bromouracil from mispairs with guanine.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The mammalian thymine DNA glycosylase (TDG) excises 5-carboxylcytosine (5caC) when paired with a guanine in a CpG sequence, in addition to mismatched bases. Here we present a complex structure of the human TDG catalytic mutant, asparagine 140 to alanine (N140A), with a 28-base pair DNA containing a G:5caC pair at pH 4.6. TDG interacts with the carboxylate moiety of target nucleotide 5caC using the side chain of asparagine 230 (N230), instead of asparagine 157 (N157) as previously reported. Mutation of either N157 or N230 residues to aspartate has minimal effect on G:5caC activity while significantly reducing activity on G:U substrate. Combination of both the asparagine-to-aspartate mutations (N157D/N230D) resulted in complete loss of activity on G:5caC while retaining measurable activity on G:U, implying that 5caC can adopt alternative conformations (either N157-interacting or N230-interacting) in the TDG active site to interact with either of the two asparagine side chain for 5caC excision.

Activity and crystal structure of human thymine DNA glycosylase mutant N140A with 5-carboxylcytosine DNA at low pH.,Hashimoto H, Zhang X, Cheng X DNA Repair (Amst). 2013 May 13. pii: S1568-7864(13)00084-0. doi:, 10.1016/j.dnarep.2013.04.003. PMID:23680598<ref>PMID:23680598</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 4jgc" style="background-color:#fffaf0;"></div>

==See Also==
*[[DNA glycosylase 3D structures|DNA glycosylase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cheng X]]
[[Category: Hashimoto H]]
[[Category: Zhang X]]