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| | <StructureSection load='6kmr' size='340' side='right'caption='[[6kmr]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='6kmr' size='340' side='right'caption='[[6kmr]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6kmr]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6KMR FirstGlance]. <br> | + | <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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</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]] 2Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TRMT112, AD-001, HSPC152, HSPC170 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), N6AMT1, C21orf127, HEMK2, PRED28 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6kmr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kmr OCA], [http://pdbe.org/6kmr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6kmr RCSB], [http://www.ebi.ac.uk/pdbsum/6kmr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6kmr 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=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> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> [[http://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> | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6kmr" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6kmr" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[DNA methyltransferase 3D structures|DNA methyltransferase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ding, J P]] | + | [[Category: Ding JP]] |
| - | [[Category: Li, W J]] | + | [[Category: Li WJ]] |
| - | [[Category: Shi, Y]] | + | [[Category: Shi Y]] |
| - | [[Category: Ye, J]] | + | [[Category: Ye J]] |
| - | [[Category: Zhang, T L]] | + | [[Category: Zhang TL]] |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Methyltransferase]]
| + | |
| - | [[Category: Polypeptide release factor erf1]]
| + | |
| - | [[Category: Protein translation]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
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).[1] [2] [3]
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[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Figaro S, Scrima N, Buckingham RH, Heurgue-Hamard V. HemK2 protein, encoded on human chromosome 21, methylates translation termination factor eRF1. FEBS Lett. 2008 Jul 9;582(16):2352-6. doi: 10.1016/j.febslet.2008.05.045. Epub, 2008 Jun 6. PMID:18539146 doi:http://dx.doi.org/10.1016/j.febslet.2008.05.045
- ↑ Fu D, Brophy JA, Chan CT, Atmore KA, Begley U, Paules RS, Dedon PC, Begley TJ, Samson LD. Human AlkB homolog ABH8 Is a tRNA methyltransferase required for wobble uridine modification and DNA damage survival. Mol Cell Biol. 2010 May;30(10):2449-59. doi: 10.1128/MCB.01604-09. Epub 2010 Mar , 22. PMID:20308323 doi:http://dx.doi.org/10.1128/MCB.01604-09
- ↑ Zorbas C, Nicolas E, Wacheul L, Huvelle E, Heurgue-Hamard V, Lafontaine DL. The human 18S rRNA base methyltransferases DIMT1L and WBSCR22-TRMT112 but not rRNA modification are required for ribosome biogenesis. Mol Biol Cell. 2015 Jun 1;26(11):2080-95. doi: 10.1091/mbc.E15-02-0073. Epub 2015, Apr 7. PMID:25851604 doi:http://dx.doi.org/10.1091/mbc.E15-02-0073
- ↑ Li W, Shi Y, Zhang T, Ye J, Ding J. Structural insight into human N6amt1-Trm112 complex functioning as a protein methyltransferase. Cell Discov. 2019 Sep 10;5:51. doi: 10.1038/s41421-019-0121-y. eCollection 2019. PMID:31636962 doi:http://dx.doi.org/10.1038/s41421-019-0121-y
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