title: Crystal structures of the human histone H4K20 methyltransferases SUV420H1 and SUV420H2.
abstract: 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.
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.forename: Alena
authors.initials: A
authors.lastname: Siarheyeva
authors.forename: Hong
authors.initials: H
authors.lastname: Zeng
authors.forename: Robert
authors.initials: R
authors.lastname: Lam
authors.forename: Aiping
authors.initials: A
authors.lastname: Dong
authors.forename: Xian-Hui
authors.initials: XH
authors.lastname: Wu
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Li
authors.forename: Matthieu
authors.initials: M
authors.lastname: Schapira
authors.forename: Masoud
authors.initials: M
authors.lastname: Vedadi
authors.forename: Jinrong
authors.initials: J
authors.lastname: Min
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D011495:Histone-Lysine N-Methyltransferase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D009154:Mutation; D012436:S-Adenosylmethionine / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity; D015032:Zinc / Q000378:metabolism
chemical_list: D006657:Histones; D012436:S-Adenosylmethionine; D011495:Histone-Lysine N-Methyltransferase; C542918:KMT5C protein, human; D015032:Zinc