Structural and functional profiling of the human histone methyltransferase SMYD3.
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...
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Public Library of Science (PLoS)
2011
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oai:doaj.org-article:8a5e03af3211429fbe1dc1ff4855df902021-11-18T06:50:14ZStructural and functional profiling of the human histone methyltransferase SMYD3.1932-620310.1371/journal.pone.0022290https://doaj.org/article/8a5e03af3211429fbe1dc1ff4855df902011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21779408/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The 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.Kenneth W ForemanMark BrownFrances ParkSpencer EmtageJune HarrissChhaya DasLi ZhuAndy CrewLee ArnoldSalam ShaabanPhilip TuckerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 7, p e22290 (2011) |
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| topic |
Medicine R Science Q |
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Medicine R Science Q Kenneth W Foreman Mark Brown Frances Park Spencer Emtage June Harriss Chhaya Das Li Zhu Andy Crew Lee Arnold Salam Shaaban Philip Tucker Structural and functional profiling of the human histone methyltransferase SMYD3. |
| description |
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. |
| format |
article |
| author |
Kenneth W Foreman Mark Brown Frances Park Spencer Emtage June Harriss Chhaya Das Li Zhu Andy Crew Lee Arnold Salam Shaaban Philip Tucker |
| author_facet |
Kenneth W Foreman Mark Brown Frances Park Spencer Emtage June Harriss Chhaya Das Li Zhu Andy Crew Lee Arnold Salam Shaaban Philip Tucker |
| author_sort |
Kenneth W Foreman |
| title |
Structural and functional profiling of the human histone methyltransferase SMYD3. |
| title_short |
Structural and functional profiling of the human histone methyltransferase SMYD3. |
| title_full |
Structural and functional profiling of the human histone methyltransferase SMYD3. |
| title_fullStr |
Structural and functional profiling of the human histone methyltransferase SMYD3. |
| title_full_unstemmed |
Structural and functional profiling of the human histone methyltransferase SMYD3. |
| title_sort |
structural and functional profiling of the human histone methyltransferase smyd3. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/8a5e03af3211429fbe1dc1ff4855df90 |
| work_keys_str_mv |
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| _version_ |
1718424305807654912 |