3RU0

Cocrystal structure of human SMYD3 with inhibitor Sinefungin bound

Summary for 3RU0

• Entry DOI: 10.2210/pdb3ru0/pdb
• Descriptor: SET and MYND domain-containing protein 3, SINEFUNGIN, ZINC ION, ... (4 entities in total)
• Functional Keywords: methyltransferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q9H7B4
• Total number of polymer chains: 2
• Total formula weight: 101853.99

Authors

Foreman, K.W.,Brown, M.,Park, F.,Emtage, S.,Harriss, J.,Das, C.,Zhu, L.,Crew, A.,Arnold, L.,Shaaban, S.,Tucker, P. (deposition date: 2011-05-04, release date: 2011-05-18, Last modification date: 2024-02-28)

Primary citation

Foreman, K.W.,Brown, M.,Park, F.,Emtage, S.,Harriss, J.,Das, C.,Zhu, L.,Crew, A.,Arnold, L.,Shaaban, S.,Tucker, P.
Structural and Functional Profiling of the Human Histone Methyltransferase SMYD3.
Plos One, 6:e22290-e22290, 2011

PubMed Abstract: The SET and MYND Domain (SMYD) proteins comprise a unique family of multi-domain SET histone methyltransferases that are implicated in human cancer progression. Here we report an analysis of the crystal structure of the full length human SMYD3 in a complex with an analog of the S-adenosyl methionine (SAM) methyl donor cofactor. The structure revealed an overall compact architecture in which the "split-SET" domain adopts a canonical SET domain fold and closely assembles with a Zn-binding MYND domain and a C-terminal superhelical 9 α-helical bundle similar to that observed for the mouse SMYD1 structure. Together, these structurally interlocked domains impose a highly confined binding pocket for histone substrates, suggesting a regulated mechanism for its enzymatic activity. Our mutational and biochemical analyses confirm regulatory roles of the unique structural elements both inside and outside the core SET domain and establish a previously undetected preference for trimethylation of H4K20.

PubMed: 21779408
DOI: 10.1371/journal.pone.0022290

Experimental method

X-RAY DIFFRACTION (1.849 Å)