title: Structure-guided design of a methyl donor cofactor that controls a viral histone H3 lysine 27 methyltransferase activity.
abstract: vSET (a viral SET domain protein) is an attractive polycomb repressive complex 2 (PRC2) surrogate to study the effect of histone H3 lysine 27 (H3K27) methylation on gene transcription, as both catalyze histone H3K27 trimethylation. To control the enzymatic activity of vSET in vivo with an engineered S-adenosyl-l-methionine (SAM) analogue as methyl donor cofactor, we have carried out structure-guided design, synthesis, and characterization of orthogonal vSET methyltransferase mutant/SAM analogue pairs using a "bump-and-hole" strategy.
authors.affiliation: Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Jiaojie
authors.initials: J
authors.lastname: Li
authors.forename: Hua
authors.initials: H
authors.lastname: Wei
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Zhou
mesh_terms: D002708:Chlorella / Q000502:physiology / Q000821:virology; D003067:Coenzymes / Q000138:chemical synthesis* / Q000494:pharmacology; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D008958:Models, Molecular; D009154:Mutation; D010247:Paramecium / Q000502:physiology; D011487:Protein Conformation; D012435:S-Adenosylhomocysteine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D003067:Coenzymes; D006657:Histones; D014764:Viral Proteins; D012435:S-Adenosylhomocysteine; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine