5TEG

Crystal structure of hSETD8 in complex with histone H4K20 norleucine mutant peptide and S-Adenosylmethionine

Summary for 5TEG

• Entry DOI: 10.2210/pdb5teg/pdb
• Descriptor: N-lysine methyltransferase KMT5A, Histone H4 mutant peptide with H4K20norleucine, S-ADENOSYLMETHIONINE, ... (4 entities in total)
• Functional Keywords: transferase, histone h4, norleucine
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus: Q9NQR1
• Total number of polymer chains: 4
• Total formula weight: 39388.70

Authors

Judge, R.A.,Petros, A.M. (deposition date: 2016-09-21, release date: 2016-12-07, Last modification date: 2024-10-23)

Primary citation

Judge, R.A.,Zhu, H.,Upadhyay, A.K.,Bodelle, P.M.,Hutchins, C.W.,Torrent, M.,Marin, V.L.,Yu, W.,Vedadi, M.,Li, F.,Brown, P.J.,Pappano, W.N.,Sun, C.,Petros, A.M.
Turning a Substrate Peptide into a Potent Inhibitor for the Histone Methyltransferase SETD8.
ACS Med Chem Lett, 7:1102-1106, 2016

PubMed Abstract: SETD8 is a histone H4-K20 methyltransferase that plays an essential role in the maintenance of genomic integrity during mitosis and in DNA damage repair, making it an intriguing target for cancer research. While some small molecule inhibitors for SETD8 have been reported, the structural binding modes for these inhibitors have not been revealed. Using the complex structure of the substrate peptide bound to SETD8 as a starting point, different natural and unnatural amino acid substitutions were tested, and a potent ( 50 nM, IC 0.33 μM) and selective norleucine containing peptide inhibitor has been obtained.

PubMed: 27994746
DOI: 10.1021/acsmedchemlett.6b00303

Experimental method

X-RAY DIFFRACTION (1.3 Å)