1q2d
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Crystal Structure of Tetrahymena GCN5 With Bound Coenzyme A and a 19-residue p53 peptide
OverviewOverview
Histone acetyltransferase (HAT) proteins often exhibit a high degree of, specificity for lysine-bearing protein substrates. We have previously, reported on the structure of the Tetrahymena Gcn5 HAT protein (tGcn5), bound to its preferred histone H3 substrate, revealing the mode of, substrate binding by the Gcn5/PCAF family of HAT proteins. Interestingly, the Gcn5/PCAF HAT family has a remarkable ability to acetylate lysine, residues within diverse cognate sites such as those found around lysines, 14, 8, and 320 of histones H3, H4, and p53, respectively. To investigate, the molecular basis for this, we now report on the crystal structures of, tGcn5 bound to 19-residue histone H4 and p53 peptides. A comparison of, these structures with tGcn5 bound to histone H3 reveals that the Gcn5/PCAF, HATs can accommodate divergent substrates by utilizing analogous, interactions with the lysine target and two C-terminal residues with a, related chemical nature, suggesting that these interactions play a general, role in Gcn5/PCAF substrate binding selectivity. In contrast, while the, histone H3 complex shows extensive interactions with tGcn5 and peptide, residues N-terminal to the target lysine, the corresponding residues in, histone H4 and p53 are disordered, suggesting that the N-terminal, substrate region plays an important role in the enhanced affinity of the, Gcn5/PCAF HAT proteins for histone H3. Together, these studies provide a, framework for understanding the substrate selectivity of HAT proteins.
About this StructureAbout this Structure
1Q2D is a Single protein structure of sequence from Tetrahymena thermophila with COA as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Molecular basis for Gcn5/PCAF histone acetyltransferase selectivity for histone and nonhistone substrates., Poux AN, Marmorstein R, Biochemistry. 2003 Dec 16;42(49):14366-74. PMID:14661947
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