Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 2.7.7.18 extracted from

  • O'Hara, J.K.; Kerwin, L.J.; Cobbold, S.A.; Tai, J.; Bedell, T.A.; Reider, P.J.; Llinas, M.
    Targeting NAD+ metabolism in the human malaria parasite Plasmodium falciparum (2014), PLoS ONE, 9, e94061.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

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

Protein Variants Comment Organism
D110A site-directed mutagenesis replacing the conserved catalytic site, inactive mutant Plasmodium falciparum

Inhibitors

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 [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

Localization Comment Organism GeneOntology No. Textmining
cytoplasm
-
Plasmodium falciparum 5737
-

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Plasmodium falciparum

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
26000
-
-
Plasmodium falciparum

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + nicotinate beta-D-ribonucleotide Plasmodium falciparum
-
diphosphate + deamido-NAD+
-
?

Organism

Organism UniProt Comment Textmining
Plasmodium falciparum Q8IE38 3D7 and D10 clones, gene PF13_0159
-

Purification (Commentary)

Purification (Comment) Organism
recombinant His6-tagged enzyme from Escherichia coli strain BL21 (RIL Codon PLUS) by nickel affinity chromatography Plasmodium falciparum

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + nicotinate beta-D-ribonucleotide
-
Plasmodium falciparum diphosphate + deamido-NAD+
-
?

Subunits

Subunits Comment Organism
? x * 26000, recombinant His6-tagged enzyme, SDS-PAGE Plasmodium falciparum

Synonyms

Synonyms Comment Organism
nicotinate mononucleotide adenylyltransferase
-
Plasmodium falciparum
PfNMNAT
-
Plasmodium falciparum

Temperature Optimum [┬░C]

Temperature Optimum [┬░C] Temperature Optimum Maximum [┬░C] Comment Organism
37
-
assay at Plasmodium falciparum

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
assay at Plasmodium falciparum

Cofactor

Cofactor Comment Organism Structure
ATP
-
Plasmodium falciparum

General Information

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