| Structural highlights
6vdb is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , |
| Gene: | SETD2, HIF1, HYPB, KIAA1732, KMT3A, SET2, HSPC069 (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[SETD2_HUMAN] Histone methyltransferase that methylates 'Lys-36' of histone H3. H3 'Lys-36' methylation represents a specific tag for epigenetic transcriptional activation. Probably plays a role in chromatin structure modulation during elongation via its interaction with hyperphosphorylated POLR2A. Binds DNA at promoters. May also act as a transcription activator that binds to promoters. Binds to the promoters of adenovirus 12 E1A gene in case of infection, possibly leading to regulate its expression.[1]
Publication Abstract from PubMed
SETD2 catalyzes methylation at lysine 36 of histone H3 and it has many disease connections. We investigated the substrate sequence specificity of SETD2 and identified nine additional peptide and one protein (FBN1) substrates. Our data showed that SETD2 strongly prefers amino acids different from those in the H3K36 sequence at several positions of its specificity profile. Based on this, we designed an optimized super-substrate containing four amino acid exchanges and show by quantitative methylation assays with SETD2 that the super-substrate peptide is methylated about 290-fold more efficiently than the H3K36 peptide. Protein methylation studies confirmed very strong SETD2 methylation of the super-substrate in vitro and in cells. We solved the structure of SETD2 with bound super-substrate peptide containing a target lysine to methionine mutation, which revealed better interactions involving three of the substituted residues. Our data illustrate that substrate sequence design can strongly increase the activity of protein lysine methyltransferases.
Sequence specificity analysis of the SETD2 protein lysine methyltransferase and discovery of a SETD2 super-substrate.,Schuhmacher MK, Beldar S, Khella MS, Brohm A, Ludwig J, Tempel W, Weirich S, Min J, Jeltsch A Commun Biol. 2020 Sep 16;3(1):511. doi: 10.1038/s42003-020-01223-6. PMID:32939018[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sun XJ, Wei J, Wu XY, Hu M, Wang L, Wang HH, Zhang QH, Chen SJ, Huang QH, Chen Z. Identification and characterization of a novel human histone H3 lysine 36-specific methyltransferase. J Biol Chem. 2005 Oct 21;280(42):35261-71. Epub 2005 Aug 22. PMID:16118227 doi:http://dx.doi.org/M504012200
- ↑ Schuhmacher MK, Beldar S, Khella MS, Brohm A, Ludwig J, Tempel W, Weirich S, Min J, Jeltsch A. Sequence specificity analysis of the SETD2 protein lysine methyltransferase and discovery of a SETD2 super-substrate. Commun Biol. 2020 Sep 16;3(1):511. doi: 10.1038/s42003-020-01223-6. PMID:32939018 doi:http://dx.doi.org/10.1038/s42003-020-01223-6
|
