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 | 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 | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
chloroplast | AtFN3K contains a chloroplast signal peptide N terminus of the kinase domain | Arabidopsis thaliana | 9507 | - |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | required | Arabidopsis thaliana | |
Mg2+ | required | Homo sapiens |
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 | UniProt | Comment | Textmining |
---|---|---|---|
Arabidopsis thaliana | - |
- |
- |
Homo sapiens | Q9H479 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
eye cancer cell | overexpression | Homo sapiens | - |
Hep-G2 cell | - |
Homo sapiens | - |
hepatoma cell | overexpression | Homo sapiens | - |
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 | 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 | 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 | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Arabidopsis thaliana | |
ATP | - |
Homo sapiens |
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 |