Description
Experimental Technique/Method:X-RAY DIFFRACTION
Resolution:1.45
Classification:TRANSFERASE
Release Date:2005-06-07
Deposition Date:2005-05-03
Revision Date:2008-04-30#2011-07-13#2017-10-11
Molecular Weight:82185.21
Macromolecule Type:Protein
Residue Count:708
Atom Site Count:5538
DOI:10.2210/pdb1zkk/pdb
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.
Resolution:1.45
Classification:TRANSFERASE
Release Date:2005-06-07
Deposition Date:2005-05-03
Revision Date:2008-04-30#2011-07-13#2017-10-11
Molecular Weight:82185.21
Macromolecule Type:Protein
Residue Count:708
Atom Site Count:5538
DOI:10.2210/pdb1zkk/pdb
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.
| Date made available | 2005 |
|---|---|
| Publisher | RCSB-PDB |