7f1e

Structure of METTL6 bound with SAMStructure of METTL6 bound with SAM

Structural highlights

7f1e is a 2 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 2.589Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

METL6_HUMAN S-adenosyl-L-methionine-dependent methyltransferase that mediates N(3)-methylcytidine modification of residue 32 of the tRNA anticodon loop of tRNA(Ser), including tRNA(Ser)(UGA) and tRNA(Ser)(GCU) (PubMed:32923617, PubMed:34922197, PubMed:34268557, PubMed:34862464). Interaction with SARS1/SerRS is required for N(3)-methylcytidine methylation (PubMed:34268557).^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

RNA modifications play important roles in mediating the biological functions of RNAs. 3-methylcytidine (m3C), albeit less abundant, is found to exist extensively in tRNAs, rRNAs and mRNAs. Human METTL6 is a m(3)C methyltransferase for tRNAs, including tRNA(SER(UGA)). We solved the structure of human METTL6 in the presence of S-adenosyl-L-methionine and found by enzyme assay that recombinant human METTL6 is active towards tRNA(SER(UGA)). Structural analysis indicated the detailed interactions between S-adenosyl-L-methionine and METTL6, and suggested potential tRNA binding region on the surface of METTL6. The structural research, complemented by biochemistry enzyme assay, will definitely shed light on the design of potent inhibitors for METTL6 in near future.

Structural basis for METTL6-mediated m3C RNA methylation.,Li S, Zhou H, Liao S, Wang X, Zhu Z, Zhang J, Xu C Biochem Biophys Res Commun. 2022 Jan 22;589:159-164. doi:, 10.1016/j.bbrc.2021.12.013. Epub 2021 Dec 13. PMID:34922197^[5]

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

References

↑ Ignatova VV, Kaiser S, Ho JSY, Bing X, Stolz P, Tan YX, Lee CL, Gay FPH, Lastres PR, Gerlini R, Rathkolb B, Aguilar-Pimentel A, Sanz-Moreno A, Klein-Rodewald T, Calzada-Wack J, Ibragimov E, Valenta M, Lukauskas S, Pavesi A, Marschall S, Leuchtenberger S, Fuchs H, Gailus-Durner V, de Angelis MH, Bultmann S, Rando OJ, Guccione E, Kellner SM, Schneider R. METTL6 is a tRNA m(3)C methyltransferase that regulates pluripotency and tumor cell growth. Sci Adv. 2020 Aug 26;6(35):eaaz4551. PMID:32923617 doi:10.1126/sciadv.aaz4551
↑ Mao XL, Li ZH, Huang MH, Wang JT, Zhou JB, Li QR, Xu H, Wang XJ, Zhou XL. Mutually exclusive substrate selection strategy by human m3C RNA transferases METTL2A and METTL6. Nucleic Acids Res. 2021 Aug 20;49(14):8309-8323. PMID:34268557 doi:10.1093/nar/gkab603
↑ Chen R, Zhou J, Liu L, Mao XL, Zhou X, Xie W. Crystal structure of human METTL6, the m(3)C methyltransferase. Commun Biol. 2021 Dec 3;4(1):1361. PMID:34862464 doi:10.1038/s42003-021-02890-9
↑ Li S, Zhou H, Liao S, Wang X, Zhu Z, Zhang J, Xu C. Structural basis for METTL6-mediated m3C RNA methylation. Biochem Biophys Res Commun. 2022 Jan 22;589:159-164. PMID:34922197 doi:10.1016/j.bbrc.2021.12.013
↑ Li S, Zhou H, Liao S, Wang X, Zhu Z, Zhang J, Xu C. Structural basis for METTL6-mediated m3C RNA methylation. Biochem Biophys Res Commun. 2022 Jan 22;589:159-164. PMID:34922197 doi:10.1016/j.bbrc.2021.12.013

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OCA

[1] Ignatova VV, Kaiser S, Ho JSY, Bing X, Stolz P, Tan YX, Lee CL, Gay FPH, Lastres PR, Gerlini R, Rathkolb B, Aguilar-Pimentel A, Sanz-Moreno A, Klein-Rodewald T, Calzada-Wack J, Ibragimov E, Valenta M, Lukauskas S, Pavesi A, Marschall S, Leuchtenberger S, Fuchs H, Gailus-Durner V, de Angelis MH, Bultmann S, Rando OJ, Guccione E, Kellner SM, Schneider R. METTL6 is a tRNA m(3)C methyltransferase that regulates pluripotency and tumor cell growth. Sci Adv. 2020 Aug 26;6(35):eaaz4551. PMID:32923617 doi:10.1126/sciadv.aaz4551

[2] Mao XL, Li ZH, Huang MH, Wang JT, Zhou JB, Li QR, Xu H, Wang XJ, Zhou XL. Mutually exclusive substrate selection strategy by human m3C RNA transferases METTL2A and METTL6. Nucleic Acids Res. 2021 Aug 20;49(14):8309-8323. PMID:34268557 doi:10.1093/nar/gkab603

[3] Chen R, Zhou J, Liu L, Mao XL, Zhou X, Xie W. Crystal structure of human METTL6, the m(3)C methyltransferase. Commun Biol. 2021 Dec 3;4(1):1361. PMID:34862464 doi:10.1038/s42003-021-02890-9

[4] Li S, Zhou H, Liao S, Wang X, Zhu Z, Zhang J, Xu C. Structural basis for METTL6-mediated m3C RNA methylation. Biochem Biophys Res Commun. 2022 Jan 22;589:159-164. PMID:34922197 doi:10.1016/j.bbrc.2021.12.013

[5] Li S, Zhou H, Liao S, Wang X, Zhu Z, Zhang J, Xu C. Structural basis for METTL6-mediated m3C RNA methylation. Biochem Biophys Res Commun. 2022 Jan 22;589:159-164. PMID:34922197 doi:10.1016/j.bbrc.2021.12.013

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