1ZKK

Crystal structure of hSET8 in ternary complex with H4 peptide (16-24) and AdoHcy

Summary for 1ZKK

• Entry DOI: 10.2210/pdb1zkk/pdb
• Descriptor: Histone-lysine N-methyltransferase, H4 lysine-20 specific, Peptide corresponding to residues 15-24 of histone H4, S-ADENOSYL-L-HOMOCYSTEINE, ... (4 entities in total)
• Functional Keywords: pseudo-knot, histone h4, beta-sheet, transferase
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: Q9NQR1
• Total number of polymer chains: 8
• Total formula weight: 82185.21

Authors

Couture, J.-F.,Collazo, E.,Brunzelle, J.S.,Trievel, R.C. (deposition date: 2005-05-03, release date: 2005-06-07, Last modification date: 2024-02-14)

Primary citation

Couture, J.-F.,Collazo, E.,Brunzelle, J.S.,Trievel, R.C.
Structural and functional analysis of SET8, a histone H4 Lys-20 methyltransferase
Genes Dev., 19:1455-1465, 2005

PubMed 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.

PubMed: 15933070
DOI: 10.1101/gad.1318405

Experimental method

X-RAY DIFFRACTION (1.45 Å)