3rq4

Crystal structure of suppressor of variegation 4-20 homolog 2

Structural highlights

3rq4 is a 1 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 1.8Å
Ligands:	EDO, SAM, UNX, ZN
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

KMT5C_HUMAN Histone methyltransferase that specifically methylates monomethylated 'Lys-20' (H4K20me1) and dimethylated 'Lys-20' (H4K20me2) of histone H4 to produce respectively dimethylated 'Lys-20' (H4K20me2) and trimethylated 'Lys-20' (H4K20me3) and thus regulates transcription and maintenance of genome integrity (PubMed:24396869, PubMed:28114273). In vitro also methylates unmodified 'Lys-20' (H4K20me0) of histone H4 and nucleosomes (PubMed:24396869). H4 'Lys-20' trimethylation represents a specific tag for epigenetic transcriptional repression. Mainly functions in pericentric heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin in these regions. KMT5C is targeted to histone H3 via its interaction with RB1 family proteins (RB1, RBL1 and RBL2) (By similarity). Facilitates TP53BP1 foci formation upon DNA damage and proficient non-homologous end-joining (NHEJ)-directed DNA repair by catalyzing the di- and trimethylation of 'Lys-20' of histone H4 (PubMed:28114273). May play a role in class switch reconbination by catalyzing the di- and trimethylation of 'Lys-20' of histone H4 (By similarity).[UniProtKB:Q6Q783]^[1] ^[2]

References

↑ Wu H, Siarheyeva A, Zeng H, Lam R, Dong A, Wu XH, Li Y, Schapira M, Vedadi M, Min J. Crystal structures of the human histone H4K20 methyltransferases SUV420H1 and SUV420H2. FEBS Lett. 2013 Nov 29;587(23):3859-68. PMID:24396869
↑ Bromberg KD, Mitchell TR, Upadhyay AK, Jakob CG, Jhala MA, Comess KM, Lasko LM, Li C, Tuzon CT, Dai Y, Li F, Eram MS, Nuber A, Soni NB, Manaves V, Algire MA, Sweis RF, Torrent M, Schotta G, Sun C, Michaelides MR, Shoemaker AR, Arrowsmith CH, Brown PJ, Santhakumar V, Martin A, Rice JC, Chiang GG, Vedadi M, Barsyte-Lovejoy D, Pappano WN. The SUV4-20 inhibitor A-196 verifies a role for epigenetics in genomic integrity. Nat Chem Biol. 2017 Mar;13(3):317-324. doi: 10.1038/nchembio.2282. Epub 2017 Jan , 23. PMID:28114273 doi:https://dx.doi.org/10.1038/nchembio.2282

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OCA

[1] Wu H, Siarheyeva A, Zeng H, Lam R, Dong A, Wu XH, Li Y, Schapira M, Vedadi M, Min J. Crystal structures of the human histone H4K20 methyltransferases SUV420H1 and SUV420H2. FEBS Lett. 2013 Nov 29;587(23):3859-68. PMID:24396869

[2] Bromberg KD, Mitchell TR, Upadhyay AK, Jakob CG, Jhala MA, Comess KM, Lasko LM, Li C, Tuzon CT, Dai Y, Li F, Eram MS, Nuber A, Soni NB, Manaves V, Algire MA, Sweis RF, Torrent M, Schotta G, Sun C, Michaelides MR, Shoemaker AR, Arrowsmith CH, Brown PJ, Santhakumar V, Martin A, Rice JC, Chiang GG, Vedadi M, Barsyte-Lovejoy D, Pappano WN. The SUV4-20 inhibitor A-196 verifies a role for epigenetics in genomic integrity. Nat Chem Biol. 2017 Mar;13(3):317-324. doi: 10.1038/nchembio.2282. Epub 2017 Jan , 23. PMID:28114273 doi:https://dx.doi.org/10.1038/nchembio.2282

[1]

[2]

3rq4

Crystal structure of suppressor of variegation 4-20 homolog 2

Structural highlights

Function

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References

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