Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary extracted from

  • Deng, S.; McTiernan, N.; Wei, X.; Arnesen, T.; Marmorstein, R.
    Molecular basis for N-terminal acetylation by human NatE and its modulation by HYPK (2020), Nat. Commun., 11, 818 .
    View publication on PubMedView publication on EuropePMC

Activating Compound

EC Number Activating Compound Comment Organism Structure
2.3.1.258 additional information NAA50 activity is increased through NAA15 tethering. hNatA significantly enhances the catalytic efficiency of hNatE Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.3.1.255 recombinant expression of N-terminally His-tagged NatA in Spodoptera frugiperda Sf9 cells, coexpression of tagged HYPK Homo sapiens
2.3.1.258 recombinant expression of hNaa15 mutants in HeLa cells, recombinant expression of N-terminally His-tagged NatA in Spodoptera frugiperda Sf9 cells, recombinant expression of His-tagged hNaa50 in Escherichia coli strain Rosetta (DE3)pLysS and strain BL21(DE3), coexpression of tagged HYPK Homo sapiens

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
2.3.1.258 purified hNatE and hNatE in complex with inhibitor HYPK, X-ray diffraction structure determination and analysis at 4.5-5.0 A resolution Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
2.3.1.255 L814P site-directed mutagenesis, the hNAA15 mutant is defective for HYPK inhibition and reduces hNatA thermostability, hNAA10 binding is not affected. The hNAA15-L814P-V5 hNatA complex shows an increased catalytic activity compared to wild-type hNatA Homo sapiens
2.3.1.255 T406Y site-directed mutagenesis, the hNAA15-T406Y-V5 hNatA mutant complex displays a decreased catalytic activity toward the hNatA substrate SESS compared to wild-type hNatA. the hNAA15 mutant can disassociate hNAA50 from hNatA in vitro, hNAA10 binding is not affected Homo sapiens
2.3.1.258 L814P site-directed mutagenesis, the hNAA15 mutant is defective for HYPK inhibition and reduces hNatA thermostability, hNAA10 binding is not affected Homo sapiens
2.3.1.258 T406Y site-directed mutagenesis, the hNAA15 mutant can disassociate hNAA50 from hNatA in vitro, hNAA10 binding is not affected Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.3.1.255 hNAA50 UniProt ID Q9GZZ1, HYPK and hNAA50 can bind to hNatA simultaneously to form a tetrameric hNatE/HYPK complex. NAA50 and HYPK exhibit negative cooperative binding to NAA15 in vitro and in human cells by inducing NAA15 shifts in opposing directions. hNAA50 and HYPK inhibit hNatA activity, and HYPK is dominant Homo sapiens
2.3.1.255 HYPK UniProt ID Q9NX55, a protein with intrinsic NAA10 catalytic subunit inhibitory activity. HYPK and hNAA50 can bind to hNatA simultaneously to form a tetrameric hNatE/HYPK complex. NAA50 and HYPK exhibit negative cooperative binding to NAA15 in vitro and in human cells by inducing NAA15 shifts in opposing directions. hNAA50 and HYPK inhibit hNatA activity, and HYPK is dominant Homo sapiens
2.3.1.258 HYPK UniProt ID Q9NX55, a protein with intrinsic NAA10 catalytic subunit inhibitory activity. HYPK and hNAA50 can bind to hNatA simultaneously to form a tetrameric hNatE/HYPK complex. hNatE displays an about 8.6fold decrease of Km, and an about 1.1fold decrease of kcat, with an overall 7.7fold increase of catalytic efficiency, compared to hNAA50. In the presence HYPK, hNatE displays an about 1.3fold decrease in Km, and an about 3.8fold decrease in kcat, with an overall 2.9fold decrease in catalytic efficiency compared to hNatE alone. The hNatE/HYPK structure reveals a negative cooperative mechanism. Over the HYPK and hNatA interaction interface within the tetrameric complex, polar interactions between HYPK-Glu74 and hNAA15-Tyr158, between the backbone carbonyl of HYPK-Thr100 and hNAA15-Lys687, between the backbone carbonyl of HYPK-Asn129 and hNAA15-Arg697, and between HYPK-Asn129 and hNAA15-Lys696 are observed Homo sapiens
2.3.1.258 additional information NAA50 and HYPK each contribute to NAA10 activity inhibition through structural alteration of the NAA10 substrate-binding site. NAA50 activity is increased through NAA15 tethering, but is inhibited by HYPK through structural alteration of the NatE substrate-binding site. hNAA50 and HYPK inhibit hNatA activity, and HYPK is dominant. The hNatE structure reveals molecular basis for enzyme crosstalk Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.3.1.258 0.0962
-
 N-terminal-L-methionyl-L-leucyl-glycyl-L-proline recombinant hNatE, pH 8.5, 37°C Homo sapiens
2.3.1.258 0.8315
-
 N-terminal-L-methionyl-L-leucyl-glycyl-L-proline recombinant hNaa50, pH 8.5, 37°C Homo sapiens

Organism

EC Number Organism UniProt Comment Textmining
2.3.1.255 Homo sapiens P41227 AND Q9BXJ9 NatA subunits Naa10 and Naa15
-
2.3.1.258 Homo sapiens Q9GZZ1 AND P41227 AND Q9BXJ9 NatE subunits Naa50, Naa10, and Naa15
-

Purification (Commentary)

EC Number Purification (Comment) Organism
2.3.1.255 recombinant His-tagged hNatA by affinity chromatography and gel filtration Homo sapiens
2.3.1.258 recombinant hNaa15 mutants, hNaa50, and hNatA by affinity chromatography and gel filtration Homo sapiens

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.3.1.255 acetyl-CoA + N-terminal L-seryl-[ESSSKSRWGRPVGRRRRPVRVYP] substrate SESS Homo sapiens CoA + H+ + N-terminal Nalpha-acetyl-L-seryl-[ESSSKSRWGRPVGRRRRPVRVYP]
-
 ?
2.3.1.258 acetyl-CoA + N-terminal-L-methionyl-L-leucyl-glycyl-L-proline
-
 Homo sapiens N-terminal-Nalpha-acetyl-L-methionyl-L-leucyl-glycyl-L-proline + CoA
-
 ir
2.3.1.258 additional information complex hNatE, comprising subunits Naa10 and Naa15 (NatA) and Naa50, is more active than hNAA50 alone Homo sapiens ?
-
-

Synonyms

EC Number Synonyms Comment Organism
2.3.1.255 N-terminal acetyltransferase A
-
 Homo sapiens
2.3.1.255 NAA10
-
 Homo sapiens
2.3.1.255 NAA15
-
 Homo sapiens
2.3.1.255 NatA
-
 Homo sapiens
2.3.1.258 N-terminal acetyltransferase E
-
 Homo sapiens
2.3.1.258 NAA10
-
 Homo sapiens
2.3.1.258 NAA15
-
 Homo sapiens
2.3.1.258 Naa50
-
 Homo sapiens
2.3.1.258 NatE
-
 Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
2.3.1.258 37
-
 assay at Homo sapiens

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
2.3.1.258 0.0515
-
 N-terminal-L-methionyl-L-leucyl-glycyl-L-proline recombinant hNatE, pH 8.5, 37°C Homo sapiens
2.3.1.258 0.0575
-
 N-terminal-L-methionyl-L-leucyl-glycyl-L-proline recombinant hNaa50, pH 8.5, 37°C Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.3.1.258 8.5
-
 assay at Homo sapiens

General Information

EC Number General Information Comment Organism
2.3.1.255 malfunction HYPK is a negative regulator for hNatA acetylation activity Homo sapiens
2.3.1.255 physiological function hNatA significantly enhances the catalytic efficiency of hNatE (EC 2.3.1.258). The hNatE complex comprises subunits Naa10 and Naa15 (NatA) and Naa50. HYPK binding to hNatE largely nullifies this effect Homo sapiens
2.3.1.258 additional information the human N-terminal acetyltransferase E (NatE) contains NAA10 and NAA50 as catalytic subunits, and NAA15 auxiliary as subunit and associates with HYPK, a protein with intrinsic NAA10 inhibitory activity. hNatE and inhibitor HYPK form a tetrameric complex. Analysis of the molecular basis for how NatE and HYPK cooperate, cryo-EM structures of human NatE and NatE/HYPK complexes, overview. NAA50 and HYPK exhibit negative cooperative binding to NAA15 in vitro and in human cells by inducing NAA15 shifts in opposing directions. HYPK and hNAA50 can bind to hNatA simultaneously to form a tetrameric hNatE/HYPK complex Homo sapiens
2.3.1.258 physiological function enzyme complex NatE co-translationally acetylates the N-terminus of half the proteome to mediate diverse biological processes, including protein half-life, localization, and interaction. The complex hNatE, comprising subunits Naa10 and Naa15 (NatA) and Naa50, is more active than hNAA50 alone Homo sapiens

kcat/KM [mM/s]

EC Number kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
2.3.1.258 0.069
-
 N-terminal-L-methionyl-L-leucyl-glycyl-L-proline recombinant hNaa50, pH 8.5, 37°C Homo sapiens
2.3.1.258 0.535
-
 N-terminal-L-methionyl-L-leucyl-glycyl-L-proline recombinant hNatE, pH 8.5, 37°C Homo sapiens