Abstract:
:SET8 (also known as PR-SET7) is a histone H4-Lys-20-specific methyltransferase that is implicated in cell-cycle-dependent transcriptional silencing and mitotic regulation in metazoans. Herein we report the crystal structure of human SET8 (hSET8) bound to a histone H4 peptide bearing Lys-20 and the product cofactor S-adenosylhomocysteine. Histone H4 intercalates in the substrate-binding cleft as an extended parallel beta-strand. Residues preceding Lys-20 in H4 engage in an extensive array of salt bridge, hydrogen bond, and van der Waals interactions with hSET8, while the C-terminal residues bind through predominantly hydrophobic interactions. Mutational analysis of both the substrate-binding cleft and histone H4 reveals that interactions with residues in the N and C termini of the H4 peptide are critical for conferring substrate specificity. Finally, analysis of the product specificity indicates that hSET8 is a monomethylase, consistent with its role in the maintenance of Lys-20 monomethylation during cell division.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Couture JF,Collazo E,Brunzelle JS,Trievel RCdoi
10.1101/gad.1318405subject
Has Abstractpub_date
2005-06-15 00:00:00pages
1455-65issue
12eissn
0890-9369issn
1549-5477pii
gad.1318405journal_volume
19pub_type
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