Cloned (Comment) | Organism |
---|---|
gene PF13_0159, phylogenetic tree, recombinant expression of His6-tagged enzyme in Escherichia coli strain BL21 (RIL Codon PLUS), recombinant expression of GFP-tagged enzyme in Plasmodium falciparum ring stage D10 culture cells | Plasmodium falciparum |
Protein Variants | Comment | Organism |
---|---|---|
D110A | site-directed mutagenesis replacing the conserved catalytic site, inactive mutant | Plasmodium falciparum |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
5-(4-bromophenyl)-N'-[(E)-(1-methyl-1H-indol-3-yl)methylidene]-4-oxopentanehydrazide | - |
Plasmodium falciparum | |
5-(4-bromophenyl)-N'-[(E)-(2,3-dimethoxynaphthalen-1-yl)methylidene]-4-oxopentanehydrazide | - |
Plasmodium falciparum | |
5-(4-fluorophenyl)-N'-[(E)-(1-methyl-1H-indol-3-yl)methylidene]-4-oxopentanehydrazide | - |
Plasmodium falciparum | |
5-[(2E)-2-(anthracen-9-ylmethylidene)hydrazinyl]-N-(4-bromophenyl)-5-oxopentanamide | - |
Plasmodium falciparum | |
5-[(2E)-2-(anthracen-9-ylmethylidene)hydrazinyl]-N-(4-fluorophenyl)-5-oxopentanamide | - |
Plasmodium falciparum | |
5-[(2E)-2-(biphenyl-4-ylmethylidene)hydrazinyl]-N-(4-bromophenyl)-5-oxopentanamide | - |
Plasmodium falciparum | |
5-[(2E)-2-(biphenyl-4-ylmethylidene)hydrazinyl]-N-(4-fluorophenyl)-5-oxopentanamide | - |
Plasmodium falciparum | |
5-[(2E)-2-[(2,3-dimethoxynaphthalen-1-yl)methylidene]hydrazinyl]-N-(4-fluorophenyl)-5-oxopentanamide | - |
Plasmodium falciparum | |
5-[(4-bromophenyl)amino]-N'-[(E)-(1-methyl-1H-indol-3-yl)methylidene]hex-5-enehydrazide | - |
Plasmodium falciparum | |
additional information | inhibitor synthesis and in vivo evaluation, MIC50 values determined using a standard SYBR green growth assay on synchronous ring stage parasites, overview | Plasmodium falciparum | |
N'-[(E)-(2,3-dimethoxynaphthalen-1-yl)methylidene]-5-(4-fluorophenyl)-4-oxopentanehydrazide | - |
Plasmodium falciparum | |
N'-[(E)-anthracen-9-ylmethylidene]-5-(2-bromophenyl)-4-oxopentanehydrazide | - |
Plasmodium falciparum | |
N'-[(E)-anthracen-9-ylmethylidene]-5-(2-hydroxyphenyl)-4-oxopentanehydrazide | - |
Plasmodium falciparum | |
N'-[(E)-anthracen-9-ylmethylidene]-5-(3-bromophenyl)-4-oxopentanehydrazide | - |
Plasmodium falciparum | |
N'-[(E)-anthracen-9-ylmethylidene]-5-(3-hydroxyphenyl)-4-oxopentanehydrazide | - |
Plasmodium falciparum | |
N'-[(E)-anthracen-9-ylmethylidene]-5-(4-bromophenyl)-4-oxopentanehydrazide | - |
Plasmodium falciparum | |
N'-[(E)-anthracen-9-ylmethylidene]-5-(4-fluorophenyl)-4-oxopentanehydrazide | - |
Plasmodium falciparum | |
N'-[(E)-anthracen-9-ylmethylidene]-5-(4-hydroxyphenyl)-4-oxopentanehydrazide | - |
Plasmodium falciparum | |
N'-[(E)-biphenyl-4-ylmethylidene]-5-(4-bromophenyl)-4-oxopentanehydrazide | - |
Plasmodium falciparum | |
N'-[(E)-biphenyl-4-ylmethylidene]-5-(4-fluorophenyl)-4-oxopentanehydrazide | - |
Plasmodium falciparum | |
N-(4-bromophenyl)-5-[(2E)-2-[(2,3-dimethoxynaphthalen-1-yl)methylidene]hydrazinyl]-5-oxopentanamide | - |
Plasmodium falciparum |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.0199 | - |
ATP | recombinant His6-tagged enzyme, pH 7.5, 37°C | Plasmodium falciparum | |
0.0358 | - |
nicotinate beta-D-ribonucleotide | recombinant His6-tagged enzyme, pH 7.5, 37°C | Plasmodium falciparum |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
cytoplasm | - |
Plasmodium falciparum | 5737 | - |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | required | Plasmodium falciparum |
Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
---|---|---|---|
26000 | - |
- |
Plasmodium falciparum |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + nicotinate beta-D-ribonucleotide | Plasmodium falciparum | - |
diphosphate + deamido-NAD+ | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Plasmodium falciparum | Q8IE38 | 3D7 and D10 clones, gene PF13_0159 | - |
Purification (Comment) | Organism |
---|---|
recombinant His6-tagged enzyme from Escherichia coli strain BL21 (RIL Codon PLUS) by nickel affinity chromatography | Plasmodium falciparum |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + nicotinate beta-D-ribonucleotide | - |
Plasmodium falciparum | diphosphate + deamido-NAD+ | - |
? |
Subunits | Comment | Organism |
---|---|---|
? | x * 26000, recombinant His6-tagged enzyme, SDS-PAGE | Plasmodium falciparum |
Synonyms | Comment | Organism |
---|---|---|
nicotinate mononucleotide adenylyltransferase | - |
Plasmodium falciparum |
PfNMNAT | - |
Plasmodium falciparum |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
assay at | Plasmodium falciparum |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.5 | - |
assay at | Plasmodium falciparum |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Plasmodium falciparum |
General Information | Comment | Organism |
---|---|---|
evolution | the enzyme is highly diverged from the human homologue, but genetically similar to bacterial NMNATs | Plasmodium falciparum |
metabolism | the essential enzyme catalyzes one step in the NAD+ pathway that synthesizes NAD+ from exogenous niacin | Plasmodium falciparum |
additional information | residue Asp110 is thought to either hydrogen bond with the adenosine monophosphate during the adenylyltransferase reaction or help with essential Mg+2 coordination during catalysis, the residue has an essential function | Plasmodium falciparum |
physiological function | the enzyme is essential for NAD+ metabolism. The enzyme is able to genetically complement the closely related Escherichia coli NMNAT enzyme | Plasmodium falciparum |