{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nIn eukaryotic cells, N-terminal acetylation is a prevalent co‐translational modification carried out by distinct N-terminal acetyltransferase (NAT) complexes. Among these, NAA50 (also known as Nat5 or San) functions as a catalytic subunit in the NatE complex and, in some contexts, is found associated with the NatA complex. While other NAT complexes—such as the hMak3‐containing NatC complex that acetylates Met–Leu N termini—modify specific subsets of nascent polypeptides"}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ", NAA50 displays a unique substrate specificity focused on peptides beginning with a methionine residue, particularly when followed by hydrophobic amino acids.\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBiochemical and structural investigations have revealed that NAA50 exhibits dual acetyltransferase activities. It not only catalyzes the transfer of an acetyl group from acetyl‐CoA to the α-amino group of its protein substrates (i.e. functioning as a NAT) but also possesses lysine acetyltransferase activity that includes autoacetylation of specific lysines—modulating its substrate selectivity. High-resolution crystal structures and NMR analyses have delineated an α-amino methionine-specific substrate pocket and an ordered Bi Bi (Theorell–Chance) mechanism in which acetyl-CoA binding induces conformational changes requisite for peptide binding."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFunctionally, NAA50 is critical for maintaining proper chromosome dynamics and genomic stability. Its activity is essential for sister chromatid cohesion and chromosome condensation during cell division; disruptions in NAA50 function can lead to p53 stabilization, impaired cohesion, and cell death. Moreover, studies have uncovered an antagonistic interplay between NAA50 and other NAT complexes—such as NatA—underscoring that distinct NAT enzymes may regulate overlapping yet opposing aspects of protein biogenesis and cell cycle control. These findings, along with the development of potent and selective inhibitors targeting NAA50, highlight its emerging potential as a therapeutic target in cancer treatment."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}, {"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Thomas Arnesen, Dave Anderson, Janniche Torsvik, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cloning and characterization of hNAT5/hSAN: an evolutionarily conserved component of the NatA protein N-alpha-acetyltransferase complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2005.12.008"}], "href": "https://doi.org/10.1016/j.gene.2005.12.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16507339"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16507339"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Fajian Hou, Chih-Wen Chu, Xiangduo Kong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The acetyltransferase activity of San stabilizes the mitotic cohesin at the centromeres in a shugoshin-independent manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200701043"}], "href": "https://doi.org/10.1083/jcb.200701043"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17502424"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17502424"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kristian K Starheim, Darina Gromyko, Rune Evjenth, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of human N alpha-terminal acetyltransferase complex C leads to p53-dependent apoptosis and aberrant human Arl8b localization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01909-08"}], "href": "https://doi.org/10.1128/MCB.01909-08"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19398576"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19398576"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Rune Evjenth, Kristine Hole, Odd A Karlsen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human Naa50p (Nat5/San) displays both protein N alpha- and N epsilon-acetyltransferase activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.001347"}], "href": "https://doi.org/10.1074/jbc.M109.001347"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19744929"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19744929"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Glen Liszczak, Thomas Arnesen, Ronen Marmorstein "}, {"type": "b", "children": [{"type": "t", "text": "Structure of a ternary Naa50p (NAT5/SAN) N-terminal acetyltransferase complex reveals the molecular basis for substrate-specific acetylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.282863"}], "href": "https://doi.org/10.1074/jbc.M111.282863"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21900231"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21900231"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Håvard Foyn, Justin E Jones, Dan Lewallen, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "N-terminal acetylome analysis reveals the specificity of Naa50 (Nat5) and suggests a kinetic competition between N-terminal acetyltransferases and methionine aminopeptidases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proteomics (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/pmic.201400575"}], "href": "https://doi.org/10.1002/pmic.201400575"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25886145"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25886145"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Ziye Rong, Zhuqing Ouyang, Robert S Magin, et al. 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