PDBsum entry 1q2c

Transferase/structural protein

PDB id: 1q2c

Contents

Protein chain

162 a.a. *

Ligands

LYS-GLY-LEU-GLY-LYS-GLY-GLY-ALA

COA

Waters ×47

* Residue conservation analysis

PDB id:

1q2c

Name:

Transferase/structural protein

Title:

Crystal structure of tetrahymena gcn5 with bound coenzyme a and a 19- residue histone h4 peptide

Structure:

Histone acetyltransferase gcn5. Chain: a. Fragment: residues 49-209, catalytic domain. Synonym: hat a1. Engineered: yes. Histone h4 peptide. Chain: b. Fragment: residues 1-19. Engineered: yes

Source:

Tetrahymena thermophila. Organism_taxid: 5911. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Synthetic: yes

Biol. unit:

Dimer (from PQS)

Resolution:

2.25Å R-factor: 0.252 R-free: 0.279

Authors:

A.N.Poux,R.Marmorstein

Key ref:

A.Clements et al. (2003). Structural basis for histone and phosphohistone binding by the GCN5 histone acetyltransferase. Mol Cell, 12, 461-473. PubMed id: 14536085 DOI: 10.1016/S1097-2765(03)00288-0

Date:

24-Jul-03 Release date: 03-Aug-04

Protein chain

Q27198  (Q27198_TETTH) -  Histone acetyltransferase GCN5 from Tetrahymena thermophila

Seq: 418 a.a.

Struc: 162 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.2.3.1.48 - histone acetyltransferase.
• Reaction: L-lysyl-[protein] + acetyl-CoA = N₆-acetyl-L-lysyl-[protein] + CoA + H⁺

L-lysyl-[protein] + acetyl-CoA = N(6)-acetyl-L-lysyl-[protein] (Bound ligand (Het Group name = COA) matches with 95.92% similarity) + CoA + H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1016/S1097-2765(03)00288-0

Mol Cell 12:461-473 (2003)

PubMed id: 14536085

Structural basis for histone and phosphohistone binding by the GCN5 histone acetyltransferase.

A.Clements, A.N.Poux, W.S.Lo, L.Pillus, S.L.Berger, R.Marmorstein.

ABSTRACT

Distinct posttranslational modifications on histones occur in specific patterns to mediate certain chromosomal events. For example, on histone H3, phosphorylation at Ser10 can enhance GCN5-mediated Lys14 acetylation to promote transcription. To gain insight into the mechanism underlying this synergism, we determined the structure of Tetrahymena GCN5 (tGCN5) and coenzyme A (CoA) bound to unmodified and Ser10-phosphorylated 19 residue histone H3 peptides (H3p19 and H3p19Pi, respectively). The tGCN5/CoA/H3p19 structure reveals that a 12 amino acid core sequence mediates extensive contacts with the protein, providing the structural basis for substrate specificity by the GCN5/PCAF family of histone acetyltransferases. Comparison with the tGCN5/CoA/H3p19Pi structure reveals that phospho-Ser10 and Thr11 mediate significant histone-protein interactions, and nucleate additional interactions distal to the phosphorylation site. Functional studies show that histone H3 Thr11 is necessary for optimal transcription at yGcn5-dependent promoters requiring Ser10 phosphorylation. Together, these studies reveal how one histone modification can modulate another to affect distinct transcriptional signals.

Selected figure(s)

Figure 3.
Figure 3. Comparison between the tGCN5/CoA/H3p19 and tGCN5/CoA/H3p19Pi Structures(A) The H3p19Pi peptide N termini. The tGCN5 blue residues represent amino acids that contact the same residues in both peptides. The tGCN5 aqua residues represent amino acids that are contacting additional residues in H3p19Pi. The tGCN5 dark green residues represent amino acids that interact with H3p19 and not with any residues in H3p19Pi. For simplicity, hydrogen-bonding interactions between H3p19Pi and tGCN5 are not shown in this figure. The residue shown in purple is a tGCN5 arginine from a symmetry-related molecule that is interacting with tGCN5 in close proximity with the peptide.(B) The H3p19Pi-peptide C termini. Hydrogen bonding between H3p19Pi and tGCN5 is represented by red dashed lines. Waters are represented as yellow spheres.(C and D) Hydrogen bonding interactions between phospho-Ser10 and tGCN5 in both conformations. The tGCN5 blue residues represent amino acids that contact Ser10 of H3p19Pi, and hydrogen bonding is represented by dashed lines.(E) Summary of the H3p19 and H3p19Pi-derived peptide-tGCN5 interactions. The gray regions of the peptide represent side chains/residues modeled in the H3p19Pi peptide and not modeled for the H3p19 peptide. The phosphate of S10P is in red. The bold bonds are shown for residues that have an increased buried surface area of at least 50 Å^2 with tGCN5/CoA when compared to the tGCN5/CoA/H3p19 interactions. The solid and dashed arrows represent tGCN5 residues that are within H-bonding and van der Waals packing distance of the peptide, respectively. Residues in blue represent amino acids that contact the same residues in both peptides. Residues in aqua represent amino acids that are contacting residues only in H3p19Pi. The tGCN5 brown residues represent amino acids that only contact S10PA. Residues in green interact with H3p19 only. The tGCN5 salmon-colored residues represent amino acids that only contact S10PB. Symbols representing residue conservation and mutational sensitivity are the same as described in the legend to Figure 1E.

Figure 6.
Figure 6. Sequence Comparisons of GCN5/PCAF Substrates^aSubstrate specificity ratios are calculated relative to H3p19^35. Substrate lysines for the sequences are identified by: ^bGrant et al., 1999; ^cKuo et al., 1996; ^dLiu et al. 1999 and Sakaguchi et al. 1998; ^eMunshi et al., 1998; ^fSartorelli et al., 1999; ^gKiernan et al., 1999.

The above figures are reprinted by permission from Cell Press: Mol Cell (2003, 12, 461-473) copyright 2003.

Figures were selected by an automated process.