6kms

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of human N6amt1-Trm112 in complex with SAM (space group I422)

Structural highlights

6kms is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.2Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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]^[1] ^[2] ^[3] ^[4] ^[5]

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^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Liu P, Nie S, Li B, Yang ZQ, Xu ZM, Fei J, Lin C, Zeng R, Xu GL. Deficiency in a glutamine-specific methyltransferase for release factor causes mouse embryonic lethality. Mol Cell Biol. 2010 Sep;30(17):4245-53. doi: 10.1128/MCB.00218-10. Epub 2010 Jul , 6. PMID:20606008 doi:http://dx.doi.org/10.1128/MCB.00218-10
↑ Ren X, Aleshin M, Jo WJ, Dills R, Kalman DA, Vulpe CD, Smith MT, Zhang L. Involvement of N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) in arsenic biomethylation and its role in arsenic-induced toxicity. Environ Health Perspect. 2011 Jun;119(6):771-7. doi: 10.1289/ehp.1002733. Epub, 2010 Dec 30. PMID:21193388 doi:http://dx.doi.org/10.1289/ehp.1002733
↑ Zhang H, Ge Y, He P, Chen X, Carina A, Qiu Y, Aga DS, Ren X. Interactive Effects of N6AMT1 and As3MT in Arsenic Biomethylation. Toxicol Sci. 2015 Aug;146(2):354-62. doi: 10.1093/toxsci/kfv101. Epub 2015 May, 20. PMID:25997655 doi:http://dx.doi.org/10.1093/toxsci/kfv101
↑ Xiao CL, Zhu S, He M, Chen, Zhang Q, Chen Y, Yu G, Liu J, Xie SQ, Luo F, Liang Z, Wang DP, Bo XC, Gu XF, Wang K, Yan GR. N(6)-Methyladenine DNA Modification in the Human Genome. Mol Cell. 2018 Jul 19;71(2):306-318.e7. doi: 10.1016/j.molcel.2018.06.015. Epub, 2018 Jul 12. PMID:30017583 doi:http://dx.doi.org/10.1016/j.molcel.2018.06.015
↑ 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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6kms"

@@ Line 3: / Line 3: @@
 <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 [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6KMS FirstGlance]. <br>
+<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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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]] 3.2&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">N6AMT1, C21orf127, HEMK2, PRED28 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TRMT112, AD-001, HSPC152, HSPC170 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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>
-<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=6kms FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kms OCA], [http://pdbe.org/6kms PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6kms RCSB], [http://www.ebi.ac.uk/pdbsum/6kms PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6kms ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[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>  [[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>
+[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 ==
@@ Line 20: / Line 19: @@
 </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: Human]]
+[[Category: Homo sapiens]]
 [[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]]

6kms

From Proteopedia

Current revision

Crystal structure of human N6amt1-Trm112 in complex with SAM (space group I422)

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox