4U9W

Crystal Structure of NatD bound to H4/H2A peptide and CoA

Summary for 4U9W

• Entry DOI: 10.2210/pdb4u9w/pdb
• Related: 4U9V 4U9X 4UA3
• Descriptor: N-alpha-acetyltransferase 40, Histone H4/H2A N-terminus, COENZYME A, ... (6 entities in total)
• Functional Keywords: acetyltransferase, gnat fold, n-terminal acetylation, acetyl-coa, transferase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 101437.68

Authors

Magin, R.S.,Liszczak, G.P.,Marmorstein, R. (deposition date: 2014-08-06, release date: 2015-01-28, Last modification date: 2024-10-16)

Primary citation

Magin, R.S.,Liszczak, G.P.,Marmorstein, R.
The Molecular Basis for Histone H4- and H2A-Specific Amino-Terminal Acetylation by NatD.
Structure, 23:332-341, 2015

PubMed Abstract: N-terminal acetylation is among the most common protein modifications in eukaryotes and is mediated by evolutionarily conserved N-terminal acetyltransferases (NATs). NatD is among the most selective NATs; its only known substrates are histones H4 and H2A, containing the N-terminal sequence SGRGK in humans. Here we characterize the molecular basis for substrate-specific acetylation by NatD by reporting its crystal structure bound to cognate substrates and performing related biochemical studies. A novel N-terminal segment wraps around the catalytic core domain to make stabilizing interactions, and the α1-α2 and β6-β7 loops adopt novel conformations to properly orient the histone N termini in the binding site. Ser1 and Arg3 of the histone make extensive contacts to highly conserved NatD residues in the substrate binding pocket, and flanking glycine residues also appear to contribute to substrate-specific binding by NatD, together defining a Ser-Gly-Arg-Gly recognition sequence. These studies have implications for understanding substrate-specific acetylation by NAT enzymes.

PubMed: 25619998
DOI: 10.1016/j.str.2014.10.025

Experimental method

X-RAY DIFFRACTION (2.49 Å)