4BUP: A Novel Route To Product Specificity In The Suv4-20 Family Of Histone H4k20 Methyltransferases

Citation:
Abstract
The delivery of site-specific post-translational modifications to histones generates an epigenetic regulatory network that directs fundamental DNA-mediated processes and governs key stages in development. Methylation of histone H4 lysine-20 has been implicated in DNA repair, transcriptional silencing, genomic stability and regulation of replication. We present the structure of the histone H4K20 methyltransferase Suv4-20h2 in complex with its histone H4 peptide substrate and S-adenosyl methionine cofactor. Analysis of the structure reveals that the Suv4-20h2 active site diverges from the canonical SET domain configuration and generates a high degree of both substrate and product specificity. Together with supporting biochemical data comparing Suv4-20h1 and Suv4-20h2, we demonstrate that the Suv4-20 family enzymes take a previously mono-methylated H4K20 substrate and generate an exclusively di-methylated product. We therefore predict that other enzymes are responsible for the tri-methylation of histone H4K20 that marks silenced heterochromatin.
PDB ID: 4BUPDownload
MMDB ID: 114188
PDB Deposition Date: 2013/6/21
Updated in MMDB: 2013/10
Experimental Method:
x-ray diffraction
Resolution: 2.17  Å
Source Organism:
Similar Structures:
Biological Unit for 4BUP: monomeric; determined by software (PISA)
Molecular Components in 4BUP
Label Count Molecule
Protein (1 molecule)
1
Histone-lysine N-methyltransferase Suv420h1(Gene symbol: Kmt5b)
Molecule annotation
Chemicals (3 molecules)
1
1
2
1
3
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.