1m1d: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1m1d.jpg|left|200px]] | [[Image:1m1d.jpg|left|200px]] | ||
<!-- | |||
The line below this paragraph, containing "STRUCTURE_1m1d", creates the "Structure Box" on the page. | |||
You may change the PDB parameter (which sets the PDB file loaded into the applet) | |||
or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |||
| | or leave the SCENE parameter empty for the default display. | ||
| | --> | ||
{{STRUCTURE_1m1d| PDB=1m1d | SCENE= }} | |||
}} | |||
'''TETRAHYMENA GCN5 WITH BOUND BISUBSTRATE ANALOG INHIBITOR''' | '''TETRAHYMENA GCN5 WITH BOUND BISUBSTRATE ANALOG INHIBITOR''' | ||
| Line 30: | Line 27: | ||
[[Category: Marmorstein, R.]] | [[Category: Marmorstein, R.]] | ||
[[Category: Poux, A N.]] | [[Category: Poux, A N.]] | ||
[[Category: | [[Category: Gcn5-related n-acetyltransferase]] | ||
[[Category: | [[Category: Histone acetyltransferase]] | ||
[[Category: | [[Category: Inhibitor complex]] | ||
[[Category: | [[Category: Transcription factor]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 00:30:58 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 00:30, 3 May 2008
TETRAHYMENA GCN5 WITH BOUND BISUBSTRATE ANALOG INHIBITOR
OverviewOverview
Histone acetyltransferases (HATs) use acetyl CoA to acetylate target lysine residues within histones and other transcription factors, such as the p53 tumor suppressor, to promote gene activation. HAT enzymes fall into subfamilies with divergence in sequence and substrate preference. Several HAT proteins have been implicated in human cancer. We have previously reported on the preparation of peptide-CoA conjugate inhibitors with distinct specificities for the p300/CBP [cAMP response element binding protein (CREB)-binding protein] or GCN5 HAT subfamilies. Here we report on the crystal structure of the GCN5 HAT bound to a peptide-CoA conjugate containing CoA covalently attached through an isopropionyl linker to Lys-14 of a 20-aa N-terminal fragment of histone H3. Surprisingly, the structure reveals that the H3 portion of the inhibitor is bound outside of the binding site for the histone substrate and that only five of the 20 aa residues of the inhibitor are ordered. Rearrangements within the C-terminal region of the GCN5 protein appear to mediate this peptide displacement. Mutational and enzymatic data support the hypothesis that the observed structure corresponds to a late catalytic intermediate. The structure also provides a structural scaffold for the design of HAT-specific inhibitors that may have therapeutic applications for the treatment of HAT-mediated cancers.
About this StructureAbout this Structure
1M1D is a Protein complex structure of sequences from Tetrahymena thermophila. Full crystallographic information is available from OCA.
ReferenceReference
Structure of the GCN5 histone acetyltransferase bound to a bisubstrate inhibitor., Poux AN, Cebrat M, Kim CM, Cole PA, Marmorstein R, Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14065-70. Epub 2002 Oct 21. PMID:12391296 Page seeded by OCA on Sat May 3 00:30:58 2008