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Information on EC 2.3.1.258 - N-terminal methionine Nalpha-acetyltransferase NatE and Organism(s) Saccharomyces cerevisiae and UniProt Accession Q08689
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2.3.1.258 N-terminal methionine Nalpha-acetyltransferase NatEIUBMB Comments
N-terminal-acetylases (NATs) catalyse the covalent attachment of an acetyl moiety from acetyl-CoA to the free alpha-amino group at the N-terminus of a protein. This irreversible modification neutralizes the positive charge at the N-terminus, makes the N-terminal residue larger and more hydrophobic, and prevents its removal by hydrolysis. It may also play a role in membrane targeting and gene silencing. NatE is found in all eukaryotic organisms and plays an important role in chromosome resolution and segregation. It specifically targets N-terminal L-methionine residues attached to Lys, Val, Ala, Tyr, Phe, Leu, Ser, and Thr. There is some substrate overlap with EC 2.3.1.256, N-terminal methionine Nalpha-acetyltransferase NatC. In addition, the acetylation of Met followed by small residues such as Ser, Thr, Ala, or Val suggests a kinetic competition between NatE and EC 3.4.11.18, methionyl aminopeptidase. The enzyme also has the activity of EC 2.3.1.48, histone acetyltransferase, and autoacetylates several of its own lysine residues.
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Word Map
- 2.3.1.258
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auxiliary
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nt-acetylation
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bisubstrate
- n-acetyltransferase
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n-termini
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drug-induced
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tunnel
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chromatid
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sister
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acetylome
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nalpha-terminal
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co-translationally
- medicine
The taxonomic range for the selected organisms is: Saccharomyces cerevisiae
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
naa50, hnata, hnaa50, naa50/san, scnaa50, nata/naa50 complex, n-terminal acetyltransferase e, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ARD1
NAA10
NAA15
Naa50
NAT1
NAT5
NatE
SAN
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Naa50
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NAT5
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PATHWAY SOURCE
PATHWAYS
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SYSTEMATIC NAME
IUBMB Comments
acetyl-CoA:N-terminal-Met-Ala/Ser/Val/Thr/Lys/Leu/Phe/Tyr-[protein] Met-Nalpha-acetyltransferase
N-terminal-acetylases (NATs) catalyse the covalent attachment of an acetyl moiety from acetyl-CoA to the free alpha-amino group at the N-terminus of a protein. This irreversible modification neutralizes the positive charge at the N-terminus, makes the N-terminal residue larger and more hydrophobic, and prevents its removal by hydrolysis. It may also play a role in membrane targeting and gene silencing. NatE is found in all eukaryotic organisms and plays an important role in chromosome resolution and segregation. It specifically targets N-terminal L-methionine residues attached to Lys, Val, Ala, Tyr, Phe, Leu, Ser, and Thr. There is some substrate overlap with EC 2.3.1.256, N-terminal methionine Nalpha-acetyltransferase NatC. In addition, the acetylation of Met followed by small residues such as Ser, Thr, Ala, or Val suggests a kinetic competition between NatE and EC 3.4.11.18, methionyl aminopeptidase. The enzyme also has the activity of EC 2.3.1.48, histone acetyltransferase, and autoacetylates several of its own lysine residues.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
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potential substrates that are less acetylated in strains lacking isoform Naa50 are: vacuolar morphogenesis protein 7, nuclear cap-binding protein subunit 2, 60S ribosomal protein L16-A, aromatic amino acid aminotransferase 1, tRNA guanosine-2'-O-methyltransferase TRM3, low specificity L-threonine aldolase
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additional information
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N-terminal acetylation (NTA) is an irreversible protein modification
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additional information
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N-terminal acetylation (NTA) is an irreversible protein modification
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
binding kinetics of ScNaa50 and ScNatA
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additional information
additional information
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binding kinetics of ScNaa50 and ScNatA
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
NatE complex subunits Naa50, Naa10 (ARD1), and Naa15 (Nat1)
UniProt
NatE complex subunits Naa50, Naa10 (ARD1), and Naa15 (Nat1)
UniProt
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
yeast Naa50 alone is defective in activity due to compromised substrate binding. Evolutionarily conserved Naa15 TY mutants can disrupt NatA-Naa50 association. Deletion of ScNaa50 shows no phenotype, while Naa50 knockout in higher organisms has been shown to perturb sister chromatid cohesion
metabolism
the enzyme is involved in the co-translational N-terminal protein modification process, overview
physiological function
additional information
evolution
the crystal structure of yeast NatA/Naa50 is used as a scaffold to uncover evolutionarily conserved catalytic crosstalk within the orthologous complexes in yeast and human, overview. NatA/Naa50 forms a stable complex through evolutionarily conserved interactions, yeast Naa50 alone is defective in activity due to compromised substrate binding. The Saccharomyces cerevisiae ScNaa15 auxiliary subunit of NatA displays a high degree of structure conservation with Schizosaccharomyces pombe SpNaa15 and human hNaa15. NatA-Naa50 from yeast and human make conserved interactions
evolution
there are seven known NAT types (NatA through NatG), each composed of one or more specific subunits and having specific substrates defined by the very first amino acid residue (serine, alanine, etc.). SpNaa50 and ScNaa50 do not contain an optimal Q/RxxGxG/A consensus acetyl-CoA binding motif
physiological function
N-terminal acetylation (NTA) is among the most widespread co-translational modifications found in eukaryotic proteins. NTA is carried out by N-terminal acetyltransferases (NATs), which catalyze the transfer of an acetyl moiety from acetyl coenzyme A to the N-terminal amino group of the nascent polypeptides as they emerge from the ribosome. NTA is an irreversible protein modification
physiological function
NatA (EC 2.3.1.255) co-translationally acetylates the N-termini of over 40% of eukaryotic proteins and can associate with another catalytic subunit, Naa50, to form a ternary NatA/Naa50 dual enzyme complex (also called NatE). NatA/Naa50 forms a stable complex through evolutionarily conserved interactions, yeast Naa50 alone is defective in activity due to compromised substrate binding, mechanism, overview
additional information
the NatA/Naa50 complex contains two catalytic subunits and one auxiliary subunit for co-translational N-terminal acetylation, structure and mechanism of acetylation by the N-terminal dual enzyme NatA/Naa50 complex, overview. NatA-Naa50 interactions promote catalytic crosstalk between Naa10 and Naa50. Shaped like a horseshoe, ScNaa15 of NatA is composed of 15 TPR motifs, which often mediate protein-protein interactions. The auxiliary subunit, consisting of a total 42 alpha-helices, serves as the binding scaffold for both catalytic subunits. ScNaa10 is completely wrapped by the Naa15 helices (from alpha11 to alpha30, encompassing residues Lys198-Gly595) with extensive interactions. Naa50 contacts both subunits of NatA
additional information
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the NatA/Naa50 complex contains two catalytic subunits and one auxiliary subunit for co-translational N-terminal acetylation, structure and mechanism of acetylation by the N-terminal dual enzyme NatA/Naa50 complex, overview. NatA-Naa50 interactions promote catalytic crosstalk between Naa10 and Naa50. Shaped like a horseshoe, ScNaa15 of NatA is composed of 15 TPR motifs, which often mediate protein-protein interactions. The auxiliary subunit, consisting of a total 42 alpha-helices, serves as the binding scaffold for both catalytic subunits. ScNaa10 is completely wrapped by the Naa15 helices (from alpha11 to alpha30, encompassing residues Lys198-Gly595) with extensive interactions. Naa50 contacts both subunits of NatA
additional information
the NatE enzyme complex is composed of the subunits Naa50 and Naa15
additional information
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the NatE enzyme complex is composed of the subunits Naa50 and Naa15
PDB
SCOP
CATH
UNIPROT
ORGANISM
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
the NatE enzyme complex is composed of the subunits Naa50 and Naa15
additional information
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the NatE enzyme complex is composed of the subunits Naa50 and Naa15
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
NatA/Naa50 complex, i.e. NatE, including full-length ScNaa15 (residues 1-854), C-terminally truncated ScNaa10 (1-226 out of 238 total residues), and full-length ScNaa50 (residues 1-176), in the presence of inositol hexaphosphate (IP6) and bi-substrate analogues for both Naa10 and Naa50, X-ray diffraction structure determination and analysis
purified recombinant ScNatA/Naa50 complex, X-ray diffraction structure determination and analysis at 2.7 A resolution
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
N-terminal analyses comparing wild-type and scNaa50 deletion strains of Saccharomyces cerevisiae
additional information
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N-terminal analyses comparing wild-type and scNaa50 deletion strains of Saccharomyces cerevisiae
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant GST-tagged hNaa50 and hNatA fromSf9 insect cells by affinity chromatography and gel filtration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant expression ofthe NatA/Naa50 complex, i.e. NatE, in Escherichia coli
recombinant overexpression of GST-tagged hNaa50 and hNatA in Spodoptera frugiperda Sf9 cells using the baculovirus transfection system
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Van Damme, P.; Hole, K.; Gevaert, K.; Arnesen, T.
N-terminal acetylome analysis reveals the specificity of Naa50 (Nat5) and suggests a kinetic competition between N-terminal acetyltransferases and methionine aminopeptidases
Proteomics
15
2436-2446
2015
Homo sapiens, Saccharomyces cerevisiae
Lyon, G.
From molecular understanding to organismal biology of N-terminal acetyltransferases
Structure
27
1053-1055
2019
Homo sapiens (Q9GZZ1 AND P41227 AND Q9BXJ9), Saccharomyces cerevisiae (Q08689 AND P41227 AND P12945), Saccharomyces cerevisiae, Saccharomyces cerevisiae ATCC 204508 (Q08689 AND P41227 AND P12945), Schizosaccharomyces pombe, Schizosaccharomyces pombe 972, Schizosaccharomyces pombe ATCC 24843
Deng, S.; Magin, R.; Wei, X.; Pan, B.; Petersson, E.; Marmorstein, R.
Structure and mechanism of acetylation by the N-terminal dual enzyme NatA/Naa50 complex
Structure
27
1057-1070.e4
2019
Homo sapiens (Q9GZZ1 AND P41227 AND Q9BXJ9), Homo sapiens, Saccharomyces cerevisiae (Q08689 AND P07347 AND P12945), Saccharomyces cerevisiae, Saccharomyces cerevisiae ATCC 204508 (Q08689 AND P07347 AND P12945), Schizosaccharomyces pombe, Schizosaccharomyces pombe 972, Schizosaccharomyces pombe ATCC 24843
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Release 2023.1 (January 2023)
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