2rba

From Proteopedia

(Difference between revisions)

Revision as of 11:14, 5 September 2018

Structure of Human Thymine DNA Glycosylase Bound to Abasic and Undamaged DNA

Structural highlights

2rba is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Gene:	TDG (Homo sapiens)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Cytosine methylation at CpG dinucleotides produces m(5)CpG, an epigenetic modification that is important for transcriptional regulation and genomic stability in vertebrate cells. However, m(5)C deamination yields mutagenic G.T mispairs, which are implicated in genetic disease, cancer, and aging. Human thymine DNA glycosylase (hTDG) removes T from G.T mispairs, producing an abasic (or AP) site, and follow-on base excision repair proteins restore the G.C pair. hTDG is inactive against normal A.T pairs, and is most effective for G.T mispairs and other damage located in a CpG context. The molecular basis of these important catalytic properties has remained unknown. Here, we report a crystal structure of hTDG (catalytic domain, hTDG(cat)) in complex with abasic DNA, at 2.8 A resolution. Surprisingly, the enzyme crystallized in a 2:1 complex with DNA, one subunit bound at the abasic site, as anticipated, and the other at an undamaged (nonspecific) site. Isothermal titration calorimetry and electrophoretic mobility-shift experiments indicate that hTDG and hTDG(cat) can bind abasic DNA with 1:1 or 2:1 stoichiometry. Kinetics experiments show that the 1:1 complex is sufficient for full catalytic (base excision) activity, suggesting that the 2:1 complex, if adopted in vivo, might be important for some other activity of hTDG, perhaps binding interactions with other proteins. Our structure reveals interactions that promote the stringent specificity for guanine versus adenine as the pairing partner of the target base and interactions that likely confer CpG sequence specificity. We find striking differences between hTDG and its prokaryotic ortholog (MUG), despite the relatively high (32%) sequence identity.

Crystal structure of human thymine DNA glycosylase bound to DNA elucidates sequence-specific mismatch recognition.,Maiti A, Morgan MT, Pozharski E, Drohat AC Proc Natl Acad Sci U S A. 2008 Jul 1;105(26):8890-5. Epub 2008 Jun 27. PMID:18587051^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Maiti A, Morgan MT, Pozharski E, Drohat AC. Crystal structure of human thymine DNA glycosylase bound to DNA elucidates sequence-specific mismatch recognition. Proc Natl Acad Sci U S A. 2008 Jul 1;105(26):8890-5. Epub 2008 Jun 27. PMID:18587051

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2rba"

@@ Line 1: / Line 1: @@
 ==Structure of Human Thymine DNA Glycosylase Bound to Abasic and Undamaged DNA==
 <StructureSection load='2rba' size='340' side='right' caption='[[2rba]], [[Resolution|resolution]] 2.79&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=3DR:1,2-DIDEOXYRIBOFURANOSE-5-PHOSPHATE'>3DR</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TDG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=2rba FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rba OCA], [http://pdbe.org/2rba PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2rba RCSB], [http://www.ebi.ac.uk/pdbsum/2rba PDBsum]</span></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=2rba FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rba OCA], [http://pdbe.org/2rba PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2rba RCSB], [http://www.ebi.ac.uk/pdbsum/2rba PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2rba ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 13: / Line 14: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/rb/2rba_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/rb/2rba_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

2rba

From Proteopedia

Revision as of 11:14, 5 September 2018

Structure of Human Thymine DNA Glycosylase Bound to Abasic and Undamaged DNA

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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