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==Crystal structure of human N6amt1-Trm112 in complex with SAM (space group P6122)== | |||
<StructureSection load='6kmr' size='340' side='right'caption='[[6kmr]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6kmr]] is a 2 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=6KMR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KMR 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]] 2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=6kmr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kmr OCA], [https://pdbe.org/6kmr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kmr RCSB], [https://www.ebi.ac.uk/pdbsum/6kmr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kmr ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/TR112_HUMAN TR112_HUMAN] Acts as an activator of both rRNA/tRNA and protein methyltransferases (PubMed:25851604). Together with methyltransferase BUD23, methylates the N(7) position of a guanine in 18S rRNA (PubMed:25851604). The heterodimer with HEMK2/N6AMT1 catalyzes N5-methylation of ETF1 on 'Gln-185', using S-adenosyl L-methionine as methyl donor (PubMed:18539146). The heterodimer with ALKBH8 catalyzes the methylation of 5-carboxymethyl uridine to 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in target tRNA species (PubMed:20308323). Involved in the pre-rRNA processing steps leading to small-subunit rRNA production (PubMed:25851604).<ref>PMID:18539146</ref> <ref>PMID:20308323</ref> <ref>PMID:25851604</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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6kmr" style="background-color:#fffaf0;"></div> | ||
[[Category: Li | |||
[[Category: | ==See Also== | ||
[[Category: | *[[DNA methyltransferase 3D structures|DNA methyltransferase 3D structures]] | ||
[[Category: Zhang | == 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]] | |||
Latest revision as of 13:37, 22 November 2023
Crystal structure of human N6amt1-Trm112 in complex with SAM (space group P6122)Crystal structure of human N6amt1-Trm112 in complex with SAM (space group P6122)
Structural highlights
FunctionTR112_HUMAN Acts as an activator of both rRNA/tRNA and protein methyltransferases (PubMed:25851604). Together with methyltransferase BUD23, methylates the N(7) position of a guanine in 18S rRNA (PubMed:25851604). The heterodimer with HEMK2/N6AMT1 catalyzes N5-methylation of ETF1 on 'Gln-185', using S-adenosyl L-methionine as methyl donor (PubMed:18539146). The heterodimer with ALKBH8 catalyzes the methylation of 5-carboxymethyl uridine to 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in target tRNA species (PubMed:20308323). Involved in the pre-rRNA processing steps leading to small-subunit rRNA production (PubMed:25851604).[1] [2] [3] Publication Abstract from PubMedDNA 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[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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