2011年6月23日

Biochemical Characterization of Human SET and MYND Domain-Containing Protein 2 Methyltransferase

Biochemical Characterization of Human SET and MYND Domain-Containing Protein 2 Methyltransferase
Biochemistry, Just Accepted Manuscript • DOI: 10.1021/bi200725p • Publication Date (Web): 16 June 2011

Background of SMYD2
A member of SMYD subfamily lysine methyl
transferases (KMTs)
Carries 'split' SET, MYND, and CTD domains
Methylates H3K36, H3K4, p53 K370 & pRb K860
Amplified in various human solid tumors
Overexpression drives proliferation of
esophageal squamous cell carcinoma

Experimental approach
SMYD2
His-SMYD2 (baculoviral expression in Sf21)
Biochemical and structural analysis to
understand the biochemical properties of SMYD2


Major conclusions
Optimal enzymatic reaction conditions: pH ~9.1, ~25 mM NaCl, 32oC,
>0.01% Tween20.
Truncation of CTD shows no appreciable influence on the enzymatic
activity, while mutations in other domains significantly impairs it.
SMYD2 coordinates three zinc ions, one of which was confirmed to be
in post-SET by X-ray crystallography.
"This work should lay the foundation for designing robust biochemical
assays for identifying SMYD2 small molecule inhibitors"

（担当：米沢）