The
 MTCY428.08
 Gene of
 Mycobacterium tuberculosis
 Codes for NAD
 +
 Synthetase

Cantoni, Rita; Branzoni, Manuela; Labó, Monica; Rizzi, Menico; Riccardi, Giovanna

doi:10.1128/jb.180.12.3218-3221.1998

Cited by 27 publications

(8 citation statements)

References 20 publications

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“…It has been known for more than 30 years that Escherichia coli NAD synthetase differs from eukaryotic NAD synthetases in that it cannot use glutamine as an ammonia source [ 7 ]. Although yeast [ 8 ] and some prokaryotic NAD synthetases [ 23 ] are glutamine dependent, they do not contain an Ntn or triad GAT domain. The glutamine-dependent NAD synthetase from Mycobacterium tuberculosis, however, contains an amino-terminal domain [ 23 ] not present in the E. coli enzyme [ 24 ].…”

Section: Domain Fusions In the Nitrilase Superfamilymentioning

confidence: 99%

Untitled

2001

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The nitrilase superfamily consists of thiol enzymes involved in natural product biosynthesis and post-translational modification in plants, animals, fungi and certain prokaryotes. On the basis of sequence similarity and the presence of additional domains, the superfamily can be classified into 13 branches, nine of which have known or deduced specificity for specific nitrile- or amide-hydrolysis or amide-condensation reactions. Genetic and biochemical analysis of the family members and their associated domains assists in predicting the localization, specificity and cell biology of hundreds of uncharacterized protein sequences.

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Section: Domain Fusions In the Nitrilase Superfamilymentioning

confidence: 99%

Untitled

2001

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“…1). The NAD + synthetase and/or its gene NadE have been iden-ti®ed in a number of prokaryotes, including Escherichia coli (Spencer & Preiss, 1967) and Bacillus subtilis (Nessi et al, 1995), and in bacterial pathogens such as Mycobacterium tuberculosis (Cantoni et al, 1998), Pseudomonas aeruginosa (Stover et al, 2000) and B. anthracis (unpublished data). Because NAD + is involved in virtually all metabolic pathways, NAD + synthetase has been suggested as a possible target for development of a new class of antibiotics (Rizzi et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

NH₃-dependent NAD⁺synthetase fromBacillus subtilisat 1 Å resolution

Symerský

Devedjiev

Moore

et al. 2002

Acta Crystallogr D Biol Cryst

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The final step of NAD+ biosynthesis includes an amide transfer to nicotinic acid adenine dinucleotide (NaAD) catalyzed by NAD+ synthetase. This enzyme was co-crystallized in microgravity with natural substrates NaAD and ATP at pH 8.5. The crystal was exposed to ammonium ions, synchrotron diffraction data were collected and the atomic model was refined anisotropically at 1 A resolution to R = 11.63%. Both binding sites are occupied by the NAD-adenylate intermediate, pyrophosphate and two magnesium ions. The atomic resolution of the structure allows better definition of non-planar peptide groups, reveals a low mean anisotropy of protein and substrate atoms and indicates the H-atom positions of the phosphoester group of the reaction intermediate. The phosphoester group is protonated at the carbonyl O atom O7N, suggesting a carbenium-ion structure stabilized by interactions with two solvent sites presumably occupied by ammonia and a water molecule. A mechanism is proposed for the second catalytic step, which includes a nucleophilic attack by the ammonia molecule on the intermediate.

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“…M. tuberculosis NAD+ synthetase is encoded by the MTCY428.08 (Rv2438c) (Cantoni et al, 1998). Both ammonia and glutamine can be used by M. tuberculosis NADS as ammonia donor, but the later is preferable.…”

Section: Nad Synthetasementioning

confidence: 99%

Comparative genomics of NAD(P) biosynthesis and novel antibiotic drug targets

Wang

Xie

2010

Journal Cellular Physiology

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NAD(P) is an indispensable cofactor for all organisms and its biosynthetic pathways are proposed as promising novel antibiotics targets against pathogens such as Mycobacterium tuberculosis. Six NAD(P) biosynthetic pathways were reconstructed by comparative genomics: de novo pathway (Asp), de novo pathway (Try), NmR pathway I (RNK-dependent), NmR pathway II (RNK-independent), Niacin salvage, and Niacin recycling. Three enzymes pivotal to the key reactions of NAD(P) biosynthesis are shared by almost all organisms, that is, NMN/NaMN adenylyltransferase (NMN/NaMNAT), NAD synthetase (NADS), and NAD kinase (NADK). They might serve as ideal broad spectrum antibiotic targets. Studies in M. tuberculosis have in part tested such hypothesis. Three regulatory factors NadR, NiaR, and NrtR, which regulate NAD biosynthesis, have been identified. M. tuberculosis NAD(P) metabolism and regulation thereof, potential drug targets and drug development are summarized in this paper.

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The MTCY428.08 Gene of Mycobacterium tuberculosis Codes for NAD ⁺ Synthetase

Cited by 27 publications

References 20 publications

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Untitled

NH₃-dependent NAD⁺synthetase fromBacillus subtilisat 1 Å resolution

Comparative genomics of NAD(P) biosynthesis and novel antibiotic drug targets

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The MTCY428.08 Gene of Mycobacterium tuberculosis Codes for NAD + Synthetase

Cited by 27 publications

References 20 publications

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NH3-dependent NAD+synthetase fromBacillus subtilisat 1 Å resolution

Comparative genomics of NAD(P) biosynthesis and novel antibiotic drug targets

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The MTCY428.08 Gene of Mycobacterium tuberculosis Codes for NAD ⁺ Synthetase

NH₃-dependent NAD⁺synthetase fromBacillus subtilisat 1 Å resolution