Information on EC 2.3.1.259 - N-terminal methionine Nalpha-acetyltransferase NatF

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The expected taxonomic range for this enzyme is: Homo sapiens

EC NUMBER
COMMENTARY hide
2.3.1.259
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RECOMMENDED NAME
GeneOntology No.
N-terminal methionine Nalpha-acetyltransferase NatF
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
acetyl-CoA + an N-terminal-L-methionyl-[transmembrane protein] = an N-terminal-Nalpha-acetyl-L-methionyl-[transmembrane protein] + CoA
show the reaction diagram
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SYSTEMATIC NAME
IUBMB Comments
acetyl-CoA:N-terminal-Met-Lys/Ser/Val/Leu/Gln/Ile/Tyr/Thr-[transmembrane 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. NatF is found only in higher eukaryotes, and is absent from yeast. Unlike other Nat systems the enzyme is located in the Golgi apparatus. It faces the cytosolic side of intracellular membranes, and specifically acetylates transmembrane proteins whose N termini face the cytosol. NatF targets N-terminal L-methionine residues attached to Lys, Ser, Val, Leu, Gln, Ile, Tyr and Thr residues.
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
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the enzyme is important for normal chromosome segregation
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + an N-terminal-L-methionyl-[transmembrane protein]
an N-terminal-Nalpha-acetyl-L-methionyl-[transmembrane protein] + CoA
show the reaction diagram
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-
-
-
?
acetyl-CoA + MAPL
CoA + N-acetyl-MAPL
show the reaction diagram
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best substrate
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-
?
acetyl-CoA + MAPLDLDRWGRPVGRRRRPVRVYP
Nalpha-acetyl-MAPLDLDRWGRPVGRRRRPVRVYP + CoA
show the reaction diagram
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-
-
-
?
acetyl-CoA + MDELFPLRWGRPVGRRRRPVRVYP
Nalpha-acetyl-MDELFPLRWGRPVGRRRRPVRVYP + CoA
show the reaction diagram
-
-
-
-
?
acetyl-CoA + MKAV
CoA + N-acetyl-MKAV
show the reaction diagram
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-
-
-
?
acetyl-CoA + MKGKEEKEGGAR
Nalpha-acetyl-MKGKEEKEGGAR + CoA
show the reaction diagram
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-
-
-
?
acetyl-CoA + MKKSYSGRWGRPVGRRRRPVRVYP
Nalpha-acetyl-MKKSYSGRWGRPVGRRRRPVRVYP + CoA
show the reaction diagram
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-
-
-
?
acetyl-CoA + MKQY
CoA + N-acetyl-MKQY
show the reaction diagram
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-
-
-
?
acetyl-CoA + MLGP
CoA + N-acetyl-MLGP
show the reaction diagram
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worst substrate
-
-
?
acetyl-CoA + MLGPEGGRWGRPVGRRRRPVRVYP
Nalpha-acetyl-MLGPEGGRWGRPVGRRRRPVRVYP + CoA
show the reaction diagram
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second highest N-terminal acetylation activity
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-
?
acetyl-CoA + MLGTEGGRWGRPVGRRRRPVRVYP
Nalpha-acetyl-MLGTEGGRWGRPVGRRRRPVRVYP + CoA
show the reaction diagram
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highest N-terminal acetylation activity
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?
acetyl-CoA + MVSM
CoA + N-acetyl-MVSM
show the reaction diagram
-
-
-
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?
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + an N-terminal-L-methionyl-[transmembrane protein]
an N-terminal-Nalpha-acetyl-L-methionyl-[transmembrane protein] + CoA
show the reaction diagram
-
-
-
-
?
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
CoA-Ac-MAPLDLD-NH2
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very potent inhibitor
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CoA-Ac-MKAVQAD-NH2
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very potent inhibitor
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desulfo-CoA
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.001
CoA-Ac-MAPLDLD-NH2
Homo sapiens;
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pH and temperature not specified in the publication
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0.00244
CoA-Ac-MKAVQAD-NH2
Homo sapiens;
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pH and temperature not specified in the publication
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0.395
desulfo-CoA
Homo sapiens;
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pH and temperature not specified in the publication
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homodimer
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x-ray crystallography
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hanging drop vapor diffusion method, using 3% (w/v) tacsimate, 0.1 M bis-Tris (pH 6.5), and 16% polyethylene glycol (PEG) 3350
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in complex with acetyl-coenzyme A or coenzyme A, hanging drop vapor diffusion method, using 10 mM Tris pH 8.0, 75 mM NaCl, 0.5% (v/v) glycerol, 3% (v/v) Tacsimate pH 4.0, and 7.5% (w/v) polyethylene glycol 3350
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
HisTrap column chromatography and Superdex 75 gel filtration
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nickel resin column chromatography and Superdex 200 gel filtration
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21 Star cells
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expressed in Escherichia coli Rosetta (DE3) pLys cells
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D81A
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the mutant shows 136.9% catalytic efficiency compared to the wild type enzyme
D81A APPLICATION
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the mutant shows about 2fold increased activity compared to the wild type enzyme
D83A
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the mutant shows about 2.8fold increased activity compared to the wild type enzyme
E37A
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the mutant shows wild type activity
E80A
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the mutant shows about 3.6fold increased activity compared to the wild type enzyme
F34A
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inactive
H138F
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the mutant is unstable and cannot be purified
H139F
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inactive
I167A
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the mutant shows an approximate 2.5 to 4fold reduction in kcat and a small increase in KM value, so the catalytic efficiency of this mutant is approximately 3fold of the wild type enzyme
I36A
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the mutant shows a 6fold reduction in catalytic efficiency compared to the wild type enzyme
I84A
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the mutant shows 200.4% catalytic efficiency compared to the wild type enzyme
K79A
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the mutant shows about 20% reduced activity compared to the wild type enzyme
K79Q
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the mutant shows about 1.8fold increased activity compared to the wild type enzyme
K79R
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the mutant shows about 1.5fold increased activity compared to the wild type enzyme
N143A
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the mutant shows about 60% reduced activity compared to the wild type enzyme
P35A
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the mutant shows a 6fold reduction in catalytic efficiency compared to the wild type enzyme
P35A/I36A/I167A
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inactive
Y164A
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the mutant shows 141.7% catalytic efficiency compared to the wild type enzyme
Y164F
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the mutant shows 154.9% catalytic efficiency compared to the wild type enzyme
Y165A
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inactive
Y165F
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the mutant has an approximately 4fold reduction in catalytic efficiency compared to the wild type enzyme
Y38A
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inactive
Y97A
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inactive
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
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development of a proteolysis-based assay, named PROMPT, i.e. PROtease assay for Membrane Protein Topology, to determine the topology of protein C-termini