View source for 6kms


==Crystal structure of human N6amt1-Trm112 in complex with SAM (space group I422)==
<StructureSection load='6kms' size='340' side='right'caption='[[6kms]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6kms]] is a 4 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=6KMS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KMS 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]] 3.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</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=6kms FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kms OCA], [https://pdbe.org/6kms PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kms RCSB], [https://www.ebi.ac.uk/pdbsum/6kms PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kms ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/N6MT1_HUMAN N6MT1_HUMAN] Methyltransferase that can methylate both proteins and DNA, and to a lower extent, arsenic (PubMed:18539146, PubMed:21193388, PubMed:30017583). Catalytic subunit of a heterodimer with TRMT112, which catalyzes N5-methylation of Glu residue of proteins with a Gly-Gln-Xaa-Xaa-Xaa-Arg motif (PubMed:18539146) (By similarity). Methylates ETF1 on 'Gln-185'; ETF1 needs to be complexed to ERF3 in its GTP-bound form to be efficiently methylated (PubMed:18539146, PubMed:20606008). Also acts as a N(6)-adenine-specific DNA methyltransferase by mediating methylation of DNA on the 6th position of adenine (N(6)-methyladenosine) (PubMed:30017583). N(6)-methyladenosine (m6A) DNA is significantly enriched in exonic regions and is associated with gene transcriptional activation (PubMed:30017583). May also play a role in the modulation of arsenic-induced toxicity by mediating the conversion of monomethylarsonous acid (3+) into the less toxic dimethylarsonic acid (PubMed:21193388, PubMed:25997655). It however only plays a limited role in arsenic metabolism compared with AS3MT (PubMed:25997655).[UniProtKB:Q6SKR2]<ref>PMID:18539146</ref> <ref>PMID:20606008</ref> <ref>PMID:21193388</ref> <ref>PMID:25997655</ref> <ref>PMID:30017583</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
DNA methylation is an important epigenetic modification in many organisms and can occur on cytosine or adenine. N(6)-methyladenine (6mA) exists widespreadly in bacterial genomes, which plays a vital role in the bacterial restriction-modification system. Recently, 6mA has also been reported to exist in the genomes of a variety of eukaryotes from unicellular organisms to metazoans. There were controversial reports on whether human N6amt1, which was originally reported as a glutamine MTase for eRF1, is a putative 6mA DNA MTase. We report here the crystal structure of human N6amt1-Trm112 in complex with cofactor SAM. Structural analysis shows that Trm112 binds to a hydrophobic surface of N6amt1 to stabilize its structure but does not directly contribute to substrate binding and catalysis. The active site and potential substrate-binding site of N6amt1 are dominantly negatively charged and thus are unsuitable for DNA binding. The biochemical data confirm that the complex cannot bind DNA and has no MTase activity for DNA, but exhibits activity for the methylation of Gln185 of eRF1. Our structural and biochemical data together demonstrate that N6amt1 is a bona fide protein MTase rather than a DNA MTase.

Structural insight into human N6amt1-Trm112 complex functioning as a protein methyltransferase.,Li W, Shi Y, Zhang T, Ye J, Ding J Cell Discov. 2019 Sep 10;5:51. doi: 10.1038/s41421-019-0121-y. eCollection 2019. PMID:31636962<ref>PMID:31636962</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6kms" style="background-color:#fffaf0;"></div>

==See Also==
*[[DNA methyltransferase 3D structures|DNA methyltransferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ding JP]]
[[Category: Li WJ]]
[[Category: Shi Y]]
[[Category: Ye J]]
[[Category: Zhang TL]]