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Literature summary for 2.3.1.255 extracted from

  • Vo, T.T.L.; Park, J.H.; Lee, E.J.; Nguyen, Y.T.K.; Han, B.W.; Nguyen, H.T.T.; Mun, K.C.; Ha, E.; Kwon, T.K.; Kim, K.W.; Jeong, C.H.; Seo, J.H.
    Characterization of lysine acetyltransferase activity of recombinant human ARD1/NAA10 (2020), Molecules, 25, 588 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
gene NAA10, recombinant expression of His-tagged ARD1/Naa10 in Escherichia coli strain BL21, recombinant expression of GST-tagged enzyme in Escherichia coli strain BL21 Homo sapiens
recombinant expression of His-tagged hARD1/NAA10 Homo sapiens

Protein Variants

Protein Variants Comment Organism
K136R site-directed mutagenesis, that lacks autoacetylation, the mutant shows wild-type NAT activity Homo sapiens
K136R site-directed mutagenesis, the non-acetylated K136R mutant shows N-terminal acetyltransferase capacity as strongly as the hARD1/NAA10 wild-type, but fails to acetylate itself Homo sapiens
R82A/Y122F site-directed mutagenesis, the mutant shows highly reduced NAT activity compared to wild-type Homo sapiens
R82A/Y122F the acetyltransferase dead DN mutant of hARD1/NAA10 almost loses its NAT activity and fails to acetylate itself. The DN mutant includes two mutations R82A and Y122F, which inhibit the binding of acetyl-CoA to hARD1/NAA10 and consequently suppresses its acetyltransferase activity Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
acetyl-CoA + an N-terminal-amino acid-[protein] Homo sapiens
-
an N-terminal-Nalpha-acetyl-amino acid-[protein] + CoA
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens P41227
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
acetylation hARD1/NAA10 undergoes autoacetylation at residue K136, which is critical to stimulate its lysine acetyltransferase (KAT) activity. Recombinant hARD1 has the tendency to lose its lysine acetylation activity in vitro. The autoacetylation is not required for NAT activity of ARD1/Naa10 Homo sapiens
acetylation hARD1/NAA10 undergoes autoacetylation, which is critical to stimulate its KAT activity. In vitro, the autoacetylation activity of purified hARD1 fails to last long Homo sapiens

Purification (Commentary)

Purification (Comment) Organism
recombinant His-tagged ARD1/Naa10 from Escherichia coli by nickel affinity chromatography, anion exchange chromatography, and gel filtration. After purification, rhARD1/NAA10 mainly exists in a high oligomeric state and has only a few monomers. Recombinant GST-tagged enzyme from Escherichia coli strain BL21 by glutathione affinity chromatography Homo sapiens
recombinant His-tagged hARD1/NAA10 enzyme by nickel affinity chromatography, with or without anion exchange chromatography, followed by gel filtration, and dialysis, rhARD1/NAA10 aggregates during purification Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
acetyl-CoA + an N-terminal-amino acid-[protein]
-
Homo sapiens an N-terminal-Nalpha-acetyl-amino acid-[protein] + CoA
-
?
acetyl-CoA + N-terminal L-aspartyl-[DDIAALRWGRPVGRRRRPVRVYP]
-
Homo sapiens CoA + H+ + N-terminal Nalpha-acetyl-L-aspartyl-[DDIAALRWGRPVGRRRRPVRVYP]
-
ir
acetyl-CoA + N-terminal L-glutamyl-[EEIAALRWGRPVGRRRRPVRVYP]
-
Homo sapiens CoA + H+ + N-terminal Nalpha-acetyl-L-glutamyl-[EEIAALRWGRPVGRRRRPVRVYP]
-
ir
additional information lysine acetyltransferase (KAT) activity of recombinant human ARD1/NAA10, overview. Arrest defective 1 (ARD1) is the only enzyme known so far to exhibit both N-terminal acetyltransferase (NAT) and N-terminal lysine acetyltransferase (KAT) activities. Only the monomeric rhARD1/NAA10 form, but not by the oligomeric form, can acetylate lysine residues of substrate proteins Homo sapiens ?
-
-
additional information recombinant hARD1/NAA10 exhibits KAT activity, which disappears soon in vitro due to enzyme oligomerization, which results in the loss of KAT activity. While oligomeric recombinant hARD1/NAA10 loses its ability for lysine acetylation, its monomeric form clearly exhibits lysine acetylation activity in vitro. Assay optimization, under optimal conditions, hARD1/NAA10 retains its KAT activity, overview Homo sapiens ?
-
-

Subunits

Subunits Comment Organism
monomer active form Homo sapiens
More size-exclusion analysis reveals that most recombinant hARD1/NAA10 form oligomers over time, resulting in the loss of KAT activity. After purification, rhARD1/NAA10 mainly exists in a high oligomeric state and has only a few monomers. The NAT activity is highest for the monomeric enzyme, about 2fold higher compared to the oligomeric enzyme and about 20% higher compared to the dimeric enzyme Homo sapiens
More the oligomeric recombinant hARD1/NAA10 loses the ability for lysine acetylation, while the monomeric form clearly shows lysine acetylation activity in vitro Homo sapiens

Synonyms

Synonyms Comment Organism
ARD1
-
Homo sapiens
arrest defective 1
-
Homo sapiens
hARD1
-
Homo sapiens
More see also EC 2.3.1.48 Homo sapiens
N(alpha)-acetyltransferase 10
-
Homo sapiens
N-terminal acetyltransferase
-
Homo sapiens
N-terminal acetyltransferase 10
-
Homo sapiens
NAA10
-
Homo sapiens
NAT
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Homo sapiens

Temperature Stability [°C]

Temperature Stability Minimum [°C] Temperature Stability Maximum [°C] Comment Organism
95
-
30 min, inactivation Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8
-
-
Homo sapiens
8
-
assay at Homo sapiens

pH Range

pH Minimum pH Maximum Comment Organism
8 9 activity range, inactive below Homo sapiens

Cofactor

Cofactor Comment Organism Structure
acetyl-CoA
-
Homo sapiens

General Information

General Information Comment Organism
malfunction inhibition of hARD1/NAA10 autoacetylation by K136R mutation induces the drop of KAT activity, but not NAT activity Homo sapiens
malfunction oligomerization results in the loss of KAT activity Homo sapiens
additional information the NAT activity is highest for the monomeric enzyme, about 2fold higher compared to the oligomeric enzyme and about 20% higher compared to the dimeric enzyme Homo sapiens
physiological function arrest defective 1 (ARD1), also known as N(alpha)-acetyltransferase 10 (NAA10) is originally identified as an N-terminal acetyltransferase (NAT) that catalyzes the acetylation of N-termini of newly synthesized peptides. Mammalian ARD1/NAA10 also plays a role as lysine acetyltransferase (KAT) that posttranslationally acetylates internal lysine residues of proteins. ARD1/NAA10 is the only enzyme with both NAT (EC 2.3.1.255) and KAT (EC 2.3.1.48) activities. NATs acetylate N-terminal residues of newly synthesized proteins from ribosomes in an irreversible manner. N-terminal acetylation is known to be closely related to protein stability, interaction, and localization. lysine acetylation catalyzed by KATs is reversibly regulated by lysine deacetyltransferases (KDACs) that remove acetyl groups from lysine residues in proteins. While acetylation neutralizes the positive charge on lysine residues, deacetylation recovers it, thereby causing a change in electronic and conformational properties of proteins. Acetylation and deacetylation of lysine residues serve as the switches that turn-on and turn-off the cellular signal pathways and regulate diverse biological events. Any unbalance between lysine acetylation and deacetylation results in the improper regulation of biological processes and may cause various types of human diseases such as cancer and neurodegeneration Homo sapiens
physiological function N-terminal acetylation catalyzed by NATs is one of the most common protein modifications in eukaryotes, affecting about 80% human proteins. In general, NATs acetylate N-terminal residues of newly synthesized proteins from ribosomes in an irreversible manner. N-terminal acetylation is known to be closely related to protein stability, interaction, and localization. Human ARD1/NAA10 expanded its' role to lysine acetyltransferase (KAT) that post-translationally acetylates internal lysine residues of proteins. Size-exclusion analysis reveals that most recombinant hARD1/NAA10 forms oligomers While oligomeric recombinant hARD1/NAA10 loses its ability for lysine acetylation, its monomeric form clearly exhibited lysine acetylation activity in vitro. In contrast to N-terminal acetylation, lysine acetylation catalyzed by KATs is reversibly regulated by lysine deacetyltransferases (KDACs) that remove acetyl groups from lysine residues in protein. hARD1 regulates a wide range of cellular functions, including cell cycle, apoptosis, migration, stress response, and differentiation. NAT and KAT activity might be independently regulated, relying on the interaction partners Homo sapiens