3OXF

Human lysine methyltransferase Smyd3 in complex with AdoHcy (Form I)

Summary for 3OXF

• Entry DOI: 10.2210/pdb3oxf/pdb
• Related: 3OXG
• Descriptor: SET and MYND domain-containing protein 3, S-ADENOSYL-L-HOMOCYSTEINE, ZINC ION, ... (4 entities in total)
• Functional Keywords: smyd proteins, mynd, set domain, histone lysine methyltransferase, histone methylation, h3k4, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : Q9H7B4
• Total number of polymer chains: 2
• Total formula weight: 101659.80

Authors

Xu, S.,Wu, J.,Sun, B.,Zhong, C.,Ding, J. (deposition date: 2010-09-21, release date: 2011-02-23, Last modification date: 2023-11-01)

Primary citation

Xu, S.,Wu, J.,Sun, B.,Zhong, C.,Ding, J.
Structural and biochemical studies of human lysine methyltransferase Smyd3 reveal the important functional roles of its post-SET and TPR domains and the regulation of its activity by DNA binding.
Nucleic Acids Res., 39:4438-4449, 2011

PubMed Abstract: The SET- and MYND-domain containing (Smyd) proteins constitute a special subfamily of the SET-containing lysine methyltransferases. Here we present the structure of full-length human Smyd3 in complex with S-adenosyl-L-homocysteine at 2.8 Å resolution. Smyd3 affords the first example that other region(s) besides the SET domain and its flanking regions participate in the formation of the active site. Structural analysis shows that the previously uncharacterized C-terminal domain of Smyd3 contains a tetratrico-peptide repeat (TPR) domain which together with the SET and post-SET domains forms a deep, narrow substrate binding pocket. Our data demonstrate the important roles of both TPR and post-SET domains in the histone lysine methyltransferase (HKMT) activity of Smyd3, and show that the hydroxyl group of Tyr239 is critical for the enzymatic activity. The characteristic MYND domain is located nearby to the substrate binding pocket and exhibits a largely positively charged surface. Further biochemical assays show that DNA binding of Smyd3 can stimulate its HKMT activity and the process may be mediated via the MYND domain through direct DNA binding.

PubMed: 21266482
DOI: 10.1093/nar/gkr019

Experimental method

X-RAY DIFFRACTION (2.82 Å)