Histone acetyltransferase 1-2 Complex (HAT1/2): Difference between revisions

[[Image:Hat1.gif|400 px|left|thumb|Figure 2. Coenzyme A (CoA, green sticks) and the histone H4 peptide substrate (pink sticks) are shown in the binding groove of HAT1. The movie was made in PyMol using 4psw.pdb, then converted to gif format using EZgif.]] The CoA molecule is buried in a deep channel in the HAT1 subunit, where the free rotation of several bonds in the [https://en.wikipedia.org/wiki/Pantetheine pantetheine] group give the molecule a bent conformation (Figure 2). The conserved Arg/Gln-X-X-Gly-X-Gly/Ala <scene name='83/834210/Newcoa/11'>signature sequence</scene> (residues 227-232) of CoA containing proteins wraps around the 5'-diphosphate moiety of the CoA. This motif also positions the negatively charged β-phosphate group of CoA at the N-terminal dipole of the helix spanning residues 230-245, further stabilizing the interaction. The <scene name='83/834210/Hydrophobic_pocket/2'>β-mercaptoethylamine group</scene> of CoA rests in the hydrophobic pocket formed by the side chains of residues Ile-217,Pro-257 and Phe-261. In the HAT1-Acetyl coenzyme A structure determined without HAT2 and the H4 substrate (PDB: 1bob) the main chain atoms of <scene name='83/834210/Acetylcoa_structure/3'>Phe220</scene> were revealed to play a critical role in binding to acetyl-CoA. The carbonyl oxygen of Phe220 hydrogen bonds to the amine of the β-mercaptoethylamine group of the co-factor, while the Phe220 amide nitrogen hydrogen bonds to the acetyl group of acetyl-CoA.<ref name=”Dutnall”>PMID:10384314</ref> The latter interaction has important implications for the mechanism as described below.