3s8p

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Crystal Structure of the SET Domain of Human Histone-Lysine N-Methyltransferase SUV420H1 In Complex With S-Adenosyl-L-Methionine

Structural highlights

3s8p 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 1.85Å
Ligands:MSE, SAM, ZN
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

KMT5B_HUMAN Histone methyltransferase that specifically trimethylates 'Lys-20' of histone H4. 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. KMT5B is targeted to histone H3 via its interaction with RB1 family proteins (RB1, RBL1 and RBL2) (By similarity). Plays a role in myogenesis by regulating the expression of target genes, such as EID3.[1]

Publication Abstract from PubMed

SUV420H1 and SUV420H2 are two highly homologous enzymes that methylate lysine 20 of histone H4 (H4K20), a mark that has been implicated in transcriptional regulation. In this study, we present the high-resolution crystal structures of human SUV420H1 and SUV420H2 in complex with SAM, and report their substrate specificity. Both methyltransferases have a unique N-terminal domain and Zn-binding post-SET domain, and prefer the monomethylated histone H4K20 as a substrate in vitro. No histone H4K20 trimethylation activity was detected by our radioactivity-based assay for either enzyme, consistent with the presence of a conserved serine residue that forms a hydrogen bond with the target lysine side-chain and limits the methylation level.

Crystal structures of the human histone H4K20 methyltransferases SUV420H1 and SUV420H2.,Wu H, Siarheyeva A, Zeng H, Lam R, Dong A, Wu XH, Li Y, Schapira M, Vedadi M, Min J FEBS Lett. 2013 Nov 29;587(23):3859-68. PMID:24396869[2]

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

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See Also

References

  1. ↑ Neguembor MV, Xynos A, Onorati MC, Caccia R, Bortolanza S, Godio C, Pistoni M, Corona DF, Schotta G, Gabellini D. FSHD muscular dystrophy region gene 1 binds Suv4-20h1 histone methyltransferase and impairs myogenesis. J Mol Cell Biol. 2013 Oct;5(5):294-307. doi: 10.1093/jmcb/mjt018. Epub 2013 May, 29. PMID:23720823 doi:http://dx.doi.org/10.1093/jmcb/mjt018
  2. ↑ 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

Contents


PDB ID 3s8p

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OCA

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