4U9V: Crystal Structure Of Natd (naa40p) Bound To Acetyl Coa

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 alpha1-alpha2 and beta6-beta7 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.
PDB ID: 4U9VDownload
MMDB ID: 126508
PDB Deposition Date: 2014/8/6
Updated in MMDB: 2017/10
Experimental Method:
x-ray diffraction
Resolution: 1.78  Å
Source Organism:
Similar Structures:
Biological Unit for 4U9V: monomeric; determined by author and by software (PISA)
Molecular Components in 4U9V
Label Count Molecule
Protein (1 molecule)
N-alpha-acetyltransferase 40(Gene symbol: NAA40)
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB