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Literature summary for 6.3.1.5 extracted from

  • Rodionova, I.A.; Schuster, B.M.; Guinn, K.M.; Sorci, L.; Scott, D.A.; Li, X.; Kheterpal, I.; Shoen, C.; Cynamon, M.; Locher, C.; Rubin, E.J.; Osterman, A.L.
    Metabolic and bactericidal effects of targeted suppression of NadD and NadE enzymes in mycobacteria (2014), mBio, 5, e00747-13 .
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
drug development NadE is a antimycobacterial drug target Mycolicibacterium smegmatis
drug development NadE is a antimycobacterial drug target Mycobacterium tuberculosis
pharmacology NadE is a antimycobacterial drug target Mycolicibacterium smegmatis
pharmacology NadE is a antimycobacterial drug target Mycobacterium tuberculosis

Protein Variants

Protein Variants Comment Organism
additional information knockout of gene nadE Mycolicibacterium smegmatis

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Mycolicibacterium smegmatis
Mg2+ required Mycobacterium tuberculosis

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + deamido-NAD+ + NH3 Mycolicibacterium smegmatis
-
AMP + diphosphate + NAD+
-
?
ATP + deamido-NAD+ + NH3 Mycobacterium tuberculosis
-
AMP + diphosphate + NAD+
-
?

Organism

Organism UniProt Comment Textmining
Mycobacterium tuberculosis A0A0U0RRS4
-
-
Mycolicibacterium smegmatis
-
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + deamido-NAD+ + NH3
-
Mycolicibacterium smegmatis AMP + diphosphate + NAD+
-
?
ATP + deamido-NAD+ + NH3
-
Mycobacterium tuberculosis AMP + diphosphate + NAD+
-
?

Synonyms

Synonyms Comment Organism
NAD synthetase
-
Mycolicibacterium smegmatis
NAD synthetase
-
Mycobacterium tuberculosis
NadE
-
Mycolicibacterium smegmatis
NadE
-
Mycobacterium tuberculosis

Cofactor

Cofactor Comment Organism Structure
ATP
-
Mycolicibacterium smegmatis
ATP
-
Mycobacterium tuberculosis

General Information

General Information Comment Organism
malfunction induced degradation of NadE enzyme shows a strong bactericidal effect which coincided with anticipated changes in relative levels of NaAD intermediate (substrate of NadE) and ultimate depletion of the NAD(H) pool. The disruption of NAD production in the cell via genetic suppression of the essential enzymes (NadD and NadE) involved in the last two steps of NAD biogenesis leads to cell death, even under dormancy conditions. Proteolytic degradation of the enzyme leads to depletion of the NAD cofactor pool, which suppresses metabolic flux through numerous NAD(P)-dependent pathways of central metabolism of carbon and energy production, phenotype, overview Mycolicibacterium smegmatis
malfunction the disruption of NAD production in the cell via genetic suppression of the essential enzymes (NadD and NadE) involved in the last two steps of NAD biogenesis leads to cell death, even under dormancy conditions. Proteolytic degradation of either target enzyme leads to depletion of the NAD cofactor pool, which suppresses metabolic flux through numerous NAD(P)-dependent pathways of central metabolism of carbon and energy production Mycobacterium tuberculosis
metabolism NaMN adenylyltransferase (NadD) and NAD synthetase (NadE) are the key enzymes of NAD biosynthesis Mycolicibacterium smegmatis
metabolism NaMN adenylyltransferase (NadD) and NAD synthetase (NadE) are the key enzymes of NAD biosynthesis Mycobacterium tuberculosis