4u9w | pdb_00004u9w
Crystal Structure of NatD bound to H4/H2A peptide and CoA
Structural highlights
FunctionNAA40_HUMAN Responsible for the acetylation of the N-terminal residues of histones H4 and H2A.[1] Publication Abstract from PubMedN-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. The Molecular Basis for Histone H4- and H2A-Specific Amino-Terminal Acetylation by NatD.,Magin RS, Liszczak GP, Marmorstein R Structure. 2015 Feb 3;23(2):332-41. doi: 10.1016/j.str.2014.10.025. Epub 2015 Jan, 22. PMID:25619998[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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