Literature summary for 2.3.1.258 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 .

Search for more literature for 2.3.1.258

Activating Compound

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

Cloned(Commentary)

Cloned (Comment)	Organism
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)

Crystallization (Comment)	Organism
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

Protein Variants	Comment	Organism
L814P	site-directed mutagenesis, the hNAA15 mutant is defective for HYPK inhibition and reduces hNatA thermostability, hNAA10 binding is not affected	Homo sapiens
T406Y	site-directed mutagenesis, the hNAA15 mutant can disassociate hNAA50 from hNatA in vitro, hNAA10 binding is not affected	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
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
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]

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

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q9GZZ1 AND P41227 AND Q9BXJ9	NatE subunits Naa50, Naa10, and Naa15	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant hNaa15 mutants, hNaa50, and hNatA by affinity chromatography and gel filtration	Homo sapiens

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
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
additional information	complex hNatE, comprising subunits Naa10 and Naa15 (NatA) and Naa50, is more active than hNAA50 alone	Homo sapiens	?	-	-

Synonyms

Synonyms	Comment	Organism
N-terminal acetyltransferase E	-	Homo sapiens
NAA10	-	Homo sapiens
NAA15	-	Homo sapiens
Naa50	-	Homo sapiens
NatE	-	Homo sapiens

Temperature Optimum [°C]

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

Turnover Number [1/s]

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

pH Optimum

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

General Information

General Information	Comment	Organism
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
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]

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

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Release 2023.1 (January 2023)