View source for 5cg9


==NgTET1 in complex with 5mC DNA in space group P3221==
<StructureSection load='5cg9' size='340' side='right' caption='[[5cg9]], [[Resolution|resolution]] 2.69&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5cg9]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Amoeba Amoeba]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CG9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CG9 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AKG:2-OXOGLUTARIC+ACID'>AKG</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=5CM:5-METHYL-2-DEOXY-CYTIDINE-5-MONOPHOSPHATE'>5CM</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5cg8|5cg8]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NAEGRDRAFT_55029 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5762 Amoeba])</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=5cg9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cg9 OCA], [http://pdbe.org/5cg9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cg9 RCSB], [http://www.ebi.ac.uk/pdbsum/5cg9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5cg9 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The family of ten-eleven translocation (Tet) dioxygenases is widely distributed across the eukaryotic tree of life, from mammals to the amoeboflagellate Naegleria gruberi. Like mammalian Tet proteins, the Naegleria Tet-like protein, NgTet1, acts on 5-methylcytosine (5mC) and generates 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) in three consecutive, Fe(II)- and alpha-ketoglutarate-dependent oxidation reactions. The two intermediates, 5hmC and 5fC, could be considered either as the reaction product of the previous enzymatic cycle or the substrate for the next cycle. Here we present a new crystal structure of NgTet1 in complex with DNA containing a 5hmC. Along with the previously solved NgTet1-5mC structure, the two complexes offer a detailed picture of the active site at individual stages of the reaction cycle. In the crystal, the hydroxymethyl (OH-CH2-) moiety of 5hmC points to the metal center, representing the reaction product of 5mC hydroxylation. The hydroxyl oxygen atom could be rotated away from the metal center, to a hydrophobic pocket formed by Ala212, Val293 and Phe295. Such rotation turns the hydroxyl oxygen atom away from the product conformation, and exposes the target CH2 towards the metal-ligand water molecule, where a dioxygen O2 molecule would occupy to initiate the next round of reaction by abstracting a hydrogen atom from the substrate. The Ala212-to-Val (A212V) mutant profoundly limits the product to 5hmC, probably because the reduced hydrophobic pocket size restricts the binding of 5hmC as a substrate.

Structure of Naegleria Tet-like dioxygenase (NgTet1) in complexes with a reaction intermediate 5-hydroxymethylcytosine DNA.,Hashimoto H, Pais JE, Dai N, Correa IR Jr, Zhang X, Zheng Y, Cheng X Nucleic Acids Res. 2015 Aug 31. pii: gkv870. PMID:26323320<ref>PMID:26323320</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5cg9" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Amoeba]]
[[Category: Cheng, X]]
[[Category: Dai, N]]
[[Category: Hashimoto, H]]
[[Category: Pais, J E]]
[[Category: Zhang, X]]
[[Category: Zheng, Y]]
[[Category: 5-methylcytosine]]
[[Category: Dioxygenase]]
[[Category: Ngtet1]]
[[Category: Oxidoreductase-dna complex]]