4lt5: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4lt5]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Naegleria_gruberi Naegleria gruberi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LT5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LT5 FirstGlance]. <br>
<table><tr><td colspan='2'>[[4lt5]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Naegleria_gruberi Naegleria gruberi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LT5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LT5 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5CM:5-METHYL-2-DEOXY-CYTIDINE-5-MONOPHOSPHATE'>5CM</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.893&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5CM:5-METHYL-2-DEOXY-CYTIDINE-5-MONOPHOSPHATE'>5CM</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4lt5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lt5 OCA], [https://pdbe.org/4lt5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lt5 RCSB], [https://www.ebi.ac.uk/pdbsum/4lt5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lt5 ProSAT]</span></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=4lt5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lt5 OCA], [https://pdbe.org/4lt5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lt5 RCSB], [https://www.ebi.ac.uk/pdbsum/4lt5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lt5 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[https://www.uniprot.org/uniprot/TET1_NAEGR TET1_NAEGR] Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), and thereby plays a role in active DNA demethylation. Also mediates subsequent conversion of 5hmC into 5-formylcytosine (5fC), and conversion of 5fC to 5-carboxylcytosine (5caC).<ref>PMID:24390346</ref> <ref>PMID:26323320</ref>  
[https://www.uniprot.org/uniprot/TET1_NAEGR TET1_NAEGR] Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), and thereby plays a role in active DNA demethylation. Also mediates subsequent conversion of 5hmC into 5-formylcytosine (5fC), and conversion of 5fC to 5-carboxylcytosine (5caC).<ref>PMID:24390346</ref> <ref>PMID:26323320</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cytosine residues in mammalian DNA occur in five forms: cytosine (C), 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). The ten-eleven translocation (Tet) dioxygenases convert 5mC to 5hmC, 5fC and 5caC in three consecutive, Fe(ii)- and alpha-ketoglutarate-dependent oxidation reactions. The Tet family of dioxygenases is widely distributed across the tree of life, including in the heterolobosean amoeboflagellate Naegleria gruberi. The genome of Naegleria encodes homologues of mammalian DNA methyltransferase and Tet proteins. Here we study biochemically and structurally one of the Naegleria Tet-like proteins (NgTet1), which shares significant sequence conservation (approximately 14% identity or 39% similarity) with mammalian Tet1. Like mammalian Tet proteins, NgTet1 acts on 5mC and generates 5hmC, 5fC and 5caC. The crystal structure of NgTet1 in complex with DNA containing a 5mCpG site revealed that NgTet1 uses a base-flipping mechanism to access 5mC. The DNA is contacted from the minor groove and bent towards the major groove. The flipped 5mC is positioned in the active-site pocket with planar stacking contacts, Watson-Crick polar hydrogen bonds and van der Waals interactions specific for 5mC. The sequence conservation between NgTet1 and mammalian Tet1, including residues involved in structural integrity and functional significance, suggests structural conservation across phyla.
Structure of a Naegleria Tet-like dioxygenase in complex with 5-methylcytosine DNA.,Hashimoto H, Pais JE, Zhang X, Saleh L, Fu ZQ, Dai N, Correa IR, Zheng Y, Cheng X Nature. 2013 Dec 25. doi: 10.1038/nature12905. PMID:24390346<ref>PMID:24390346</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4lt5" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>

Latest revision as of 15:21, 1 March 2024

Structure of a Naegleria Tet-like dioxygenase in complex with 5-methylcytosine DNAStructure of a Naegleria Tet-like dioxygenase in complex with 5-methylcytosine DNA

Structural highlights

4lt5 is a 3 chain structure with sequence from Naegleria gruberi. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.893Å
Ligands:, , , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TET1_NAEGR Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), and thereby plays a role in active DNA demethylation. Also mediates subsequent conversion of 5hmC into 5-formylcytosine (5fC), and conversion of 5fC to 5-carboxylcytosine (5caC).[1] [2]

References

  1. Hashimoto H, Pais JE, Zhang X, Saleh L, Fu ZQ, Dai N, Correa IR, Zheng Y, Cheng X. Structure of a Naegleria Tet-like dioxygenase in complex with 5-methylcytosine DNA. Nature. 2013 Dec 25. doi: 10.1038/nature12905. PMID:24390346 doi:http://dx.doi.org/10.1038/nature12905
  2. Hashimoto H, Pais JE, Dai N, Correa IR Jr, Zhang X, Zheng Y, Cheng X. Structure of Naegleria Tet-like dioxygenase (NgTet1) in complexes with a reaction intermediate 5-hydroxymethylcytosine DNA. Nucleic Acids Res. 2015 Aug 31. pii: gkv870. PMID:26323320 doi:http://dx.doi.org/10.1093/nar/gkv870

4lt5, resolution 2.89Å

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