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Literature summary for 2.7.1.171 extracted from

  • Shrestha, S.; Katiyar, S.; Sanz-Rodriguez, C.E.; Kemppinen, N.R.; Kim, H.W.; Kadirvelraj, R.; Panagos, C.; Keyhaninejad, N.; Colonna, M.; Chopra, P.; Byrne, D.P.; Boons, G.J.; van der Knaap, E.; Eyers, P.A.; Edison, A.S.; Wood, Z.A.; Kannan, N.
    A redox-active switch in fructosamine-3-kinases expands the regulatory repertoire of the protein kinase superfamily (2020), Sci. Signal., 13, eaax6313 .
    View publication on PubMed

Activating Compound

Activating Compound Comment Organism Structure
DTT the activity of the dimer species increases nearly 40fold in the presence of 2 mM the reductant, while the monomer species is active but insensitive to DTT Arabidopsis thaliana
GSH reduced glutathione, activity of the dimer species increases with increasing concentration of the physiological reductant Arabidopsis thaliana
additional information the AtFN3K wild-type dimer is activated by redox agents Arabidopsis thaliana

Protein Variants

Protein Variants Comment Organism
C236A site-directed mutagenesis, similar to the wild-type enzyme, both dimeric and monomeric forms are detected Arabidopsis thaliana
C236S site-directed mutagenesis, similar to the wild-type enzyme, both dimeric and monomeric forms are detected Arabidopsis thaliana
C32A site-directed mutagenesis, similar to the wild-type enzyme, both dimeric and monomeric forms are detected Arabidopsis thaliana
C32A/C236A/C196A site-directed mutagenesis, similar to the wild-type enzyme, both dimeric and monomeric forms are detected Arabidopsis thaliana
C32S site-directed mutagenesis, similar to the wild-type enzyme, both dimeric and monomeric forms are detected Arabidopsis thaliana

Localization

Localization Comment Organism GeneOntology No. Textmining
chloroplast AtFN3K contains a chloroplast signal peptide N terminus of the kinase domain Arabidopsis thaliana 9507
-

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Arabidopsis thaliana
Mg2+ required Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + [protein]-N6-D-fructosyl-L-lysine Arabidopsis thaliana
-
ADP + [protein]-N6-(3-O-phospho-D-fructosyl)-L-lysine
-
?
ATP + [protein]-N6-D-fructosyl-L-lysine Homo sapiens
-
ADP + [protein]-N6-(3-O-phospho-D-fructosyl)-L-lysine
-
?

Organism

Organism UniProt Comment Textmining
Arabidopsis thaliana
-
-
-
Homo sapiens Q9H479
-
-

Source Tissue

Source Tissue Comment Organism Textmining
eye cancer cell overexpression Homo sapiens
-
Hep-G2 cell
-
Homo sapiens
-
hepatoma cell overexpression Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + [protein]-N6-D-fructosyl-L-lysine
-
Arabidopsis thaliana ADP + [protein]-N6-(3-O-phospho-D-fructosyl)-L-lysine
-
?
ATP + [protein]-N6-D-fructosyl-L-lysine
-
Homo sapiens ADP + [protein]-N6-(3-O-phospho-D-fructosyl)-L-lysine
-
?

Subunits

Subunits Comment Organism
dimer
-
Homo sapiens
dimer the crystal structure of the FN3K homologue from Arabidopsis thaliana reveals that it forms an unexpected strand-exchange dimer in which the ATP-binding P-loop and adjoining beta-strands are swapped between two chains in the dimer. This dimeric configuration is characterized by strained interchain disulfide bonds that stabilize the P-loop in an extended conformation. In the AtFN3K dimer, the substrate-binding lobes are covalently tethered to create a unique interface, presumably for phosphorylating ketosamine and related substrates. AtFN3K can dimerize without the cysteines Arabidopsis thaliana
monomer
-
Arabidopsis thaliana
monomer
-
Homo sapiens
More FN3K adopts a protein kinase fold. Structure-function analysis and comparisons, overview Homo sapiens
More FN3K adopts a protein kinase fold. The wild-type and mutant enzymes show both dimeric and monomeric forms, structure-function analysis and comparisons, overview Arabidopsis thaliana

Synonyms

Synonyms Comment Organism
AtFN3K
-
Arabidopsis thaliana
FN3K
-
Arabidopsis thaliana
FN3K
-
Homo sapiens
fructosamine-3-kinase
-
Arabidopsis thaliana
fructosamine-3-kinase
-
Homo sapiens
HsFN3K
-
Homo sapiens

Cofactor

Cofactor Comment Organism Structure
ATP
-
Arabidopsis thaliana
ATP
-
Homo sapiens

General Information

General Information Comment Organism
evolution fructosamine-3-kinases belong to the large superfamily of protein kinase-like (PKL) enzymes. The strained disulfides in the dimeric Arabidosis thalina enzyme function as redox switches to reversibly regulate the activity and dimerization of FN3K. Human FN3K, which contains an equivalent P-loop Cys, is also redox sensitive, whereas ancestral bacterial FN3K homologues, which lack a P-loop Cys, are not. Redox control mediated by the P-loop Cys is an ancient mechanism of FN3K regulation that emerged progressively during FN3K evolution from bacteria to humans. Redox regulation seem to have evolved in FN3K homologues in response to changing cellular redox conditions Arabidopsis thaliana
evolution fructosamine-3-kinases belong to the large superfamily of protein kinase-like (PKL) enzymes. The strained disulfides in the dimeric Arabidosis thalina enzyme function as redox switches to reversibly regulate the activity and dimerization of FN3K. Human FN3K, which contains an equivalent P-loop Cys, is also redox sensitive, whereas ancestral bacterial FN3K homologues, which lack a P-loop Cys, are not. Redox control mediated by the P-loop Cys is an ancient mechanism of FN3K regulation that emerged progressively during FN3K evolution from bacteria to humans. Redox regulation seems to have evolved in FN3K homologues in response to changing cellular redox conditions Homo sapiens
malfunction FN3K CRISPR knockout alters redox-sensitive cellular metabolites Homo sapiens
malfunction removal of the chloroplast signal peptide results in the localization of AtFN3K in different cellular compartments, including nucleus and mitochondria. FN3K CRISPR knockout alters redox-sensitive cellular metabolites Arabidopsis thaliana
additional information the strained disulfides in the dimeric Arabidosis thalina enzyme function as redox switches to reversibly regulate the activity and dimerization of FN3K. Critical role for the ATP-binding P-loop in the redox regulation of FN3Ks. HsFN3K, in which the P-loop Cys is conserved, is redox-regulated and displayed altered oligomerization when proliferating cells are exposed to acute oxidative stress. Structure-function analysis, overview Homo sapiens
additional information the strained disulfides in the dimeric Arabidosis thalina enzyme function as redox switches to reversibly regulate the activity and dimerization of FN3K. Critical role for the ATP-binding P-loop in the redox regulation of FN3Ks. The P-loop is stabilized in an extended conformation by a Cys-mediated disulfide bond connecting two chains to form a covalently linked dimer in which the reduction of disulfides results in AtFN3K activation. Structure-function analysis, overview Arabidopsis thaliana