Escherichia coli K-12 substr. MG1655 Enzyme: nicotinate-mononucleotide adenylyltransferase

Gene: nadD Accession Numbers: G6350 (EcoCyc), b0639, ECK0632

Synonyms: ybeN, fusB

Regulation Summary Diagram: ?

Regulation summary diagram for nadD

Nicotinate-mononucleotide adenylyltransferase is an essential enzyme involved in both de novo biosynthesis and salvage of NAD+ and NADPH. Both nicotinate mononucleotide (NMN) and nicotinamide mononucleotide (NAMN) are substrates, but the rate of adenylation of NMN is at least 20 times faster than that of NAMN [Mehl00].

Crystal structures of the enzyme alone and in a complex with deamido-NAD have been solved and show that ligand binding causes conformational changes in regions surrounding the active site [Zhang02c].

The nadD72 mutant allele was first isolated as a spontaneous temperature-sensitive mutation that leads to higher tolerance to fusidic acid (hence it was originally named fusB). The mutant phenotype is pleiotropic [Isaksson78]. Further characterization of this mutation showed it to be an allele of nadD with a frameshift mutation that leads to a change in the C terminus of the NadD protein. The mutant synthesizes very little NAD+ and NADPH at the permissive temperature and essentially none at the non-permissive temperature [Stancek03]. The newly isolated nadD74 allele causes an amino acid change in the ATP-binding site of NadD. On miminal medium, the mutant shows temperature sensitivity due to a reduction in NAD+ synthesis; at the permissive temperature, NAD+ synthesis is reduced, but sufficient to support normal growth [Stancek03]. Additional mutants in nadD have been isolated and characterized [Stancek05].

nadD is essential for growth [Gerdes02, Stancek05].

Locations: cytosol

Map Position: [669,154 <- 669,795] (14.42 centisomes, 52°)
Length: 642 bp / 213 aa

Molecular Weight of Polypeptide: 24.528 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0002187 , EchoBASE:EB3030 , EcoGene:EG13241 , EcoliWiki:b0639 , ModBase:P0A752 , OU-Microarray:b0639 , PortEco:nadD , PR:PRO_000023334 , Protein Model Portal:P0A752 , RefSeq:NP_415172 , RegulonDB:G6350 , SMR:P0A752 , String:511145.b0639 , UniProt:P0A752

Relationship Links: InterPro:IN-FAMILY:IPR004821 , InterPro:IN-FAMILY:IPR005248 , InterPro:IN-FAMILY:IPR014729 , Panther:IN-FAMILY:PTHR12039 , PDB:Structure:1K4K , PDB:Structure:1K4M , Pfam:IN-FAMILY:PF01467

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

GO Terms:

Biological Process: GO:0034355 - NAD salvage Inferred from experiment [Stancek03]
GO:0034628 - 'de novo' NAD biosynthetic process from aspartate Inferred from experiment [Stancek03]
GO:0009058 - biosynthetic process Inferred by computational analysis [GOA01a]
GO:0009435 - NAD biosynthetic process Inferred by computational analysis [UniProtGOA12, GOA06, GOA01a]
GO:0019363 - pyridine nucleotide biosynthetic process Inferred by computational analysis [UniProtGOA11a]
Molecular Function: GO:0004515 - nicotinate-nucleotide adenylyltransferase activity Inferred from experiment Inferred by computational analysis [GOA06, GOA01, Mehl00]
GO:0000166 - nucleotide binding Inferred by computational analysis [UniProtGOA11a]
GO:0003824 - catalytic activity Inferred by computational analysis [GOA01a]
GO:0005524 - ATP binding Inferred by computational analysis [UniProtGOA11a]
GO:0016740 - transferase activity Inferred by computational analysis [UniProtGOA11a]
GO:0016779 - nucleotidyltransferase activity Inferred by computational analysis [UniProtGOA11a, GOA01a]
Cellular Component: GO:0005829 - cytosol Inferred by computational analysis [DiazMejia09]

MultiFun Terms: metabolism biosynthesis of building blocks cofactors, small molecule carriers nicotinamide adenine dinucleotide

Essentiality data for nadD knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox No 37 Aerobic 7   No [Baba06, Comment 2]

Last-Curated ? 01-Aug-2008 by Keseler I , SRI International

Enzymatic reaction of: nicotinate-mononucleotide adenylyltransferase

Synonyms: deamido-NAD+ pyrophosphorylase, nicotinic acid adenine dinucleotide pyrophosphorylase, deamido-DPN pyrophosphorylase, ATP:nicotinate-ribonucleotide adenylyltransferase, nicotinic acid mononucleotide adenylyltransferase

EC Number:

ATP + β-nicotinate D-ribonucleotide + H+ <=> nicotinate adenine dinucleotide + diphosphate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is physiologically favored in the direction shown.

Alternative Substrates for β-nicotinate D-ribonucleotide [Comment 3 ]: β-nicotinamide D-ribonucleotide [Mehl00 ]

In Pathways: aspartate superpathway , NAD biosynthesis I (from aspartate) , NAD salvage pathway I

The enzyme is able to catalyze the reverse reaction as well in vitro [Mehl00]; however, it seems unlikely that the diphosphate concentration in vivo is high enough to allow formation of ATP and nicotinate mononucleotide.

Partial purification and characterization of the enzyme in [Dahmen67] used E. coli B.

Cofactors or Prosthetic Groups: Mg2+ [Imsande61]

Activators (Unknown Mechanism): K+ [Dahmen67]

Kinetic Parameters:

Km (μM)
nicotinate adenine dinucleotide
[Lau09, BRENDA14]
β-nicotinate D-ribonucleotide
[Dahmen67, BRENDA14]
β-nicotinate D-ribonucleotide

pH(opt): 7.5 [Imsande61]

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Unit:

Transcription-unit diagram


Markus Krummenacker on Tue Oct 14, 1997:
Gene object created from Blattner lab Genbank (v. M52) entry.


Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014."

Dahmen67: Dahmen W, Webb B, Preiss J (1967). "The deamido-diphosphopyridine nucleotide and diphosphopyridine nucleotide pyrophosphorylases of Escherichia coli and yeast." Arch Biochem Biophys 1967;120(2);440-50. PMID: 4291828

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Gerdes02: Gerdes SY, Scholle MD, D'Souza M, Bernal A, Baev MV, Farrell M, Kurnasov OV, Daugherty MD, Mseeh F, Polanuyer BM, Campbell JW, Anantha S, Shatalin KY, Chowdhury SA, Fonstein MY, Osterman AL (2002). "From genetic footprinting to antimicrobial drug targets: examples in cofactor biosynthetic pathways." J Bacteriol 184(16);4555-72. PMID: 12142426

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

Imsande61: Imsande J (1961). "Pathway of diphosphopyridine nucleotide biosynthesis in Escherichia coli." J Biol Chem 1961;236(5):1494-1497. PMID: 13717628

Isaksson78: Isaksson LA, Takata R (1978). "The temperature sensitive mutant 72c. I. Pleiotropic growth behaviour and changed response to some antibiotics and mutations in the transcription or translation apparatus." Mol Gen Genet 161(1);9-14. PMID: 353503

Lau09: Lau C, Niere M, Ziegler M (2009). "The NMN/NaMN adenylyltransferase (NMNAT) protein family." Front Biosci (Landmark Ed) 14;410-31. PMID: 19273075

Mehl00: Mehl RA, Kinsland C, Begley TP (2000). "Identification of the Escherichia coli nicotinic acid mononucleotide adenylyltransferase gene." J Bacteriol 2000;182(15);4372-4. PMID: 10894752

Stancek03: Stancek M, Isaksson LA, Ryden-Aulin M (2003). "fusB is an allele of nadD, encoding nicotinate mononucleotide adenylyltransferase in Escherichia coli." Microbiology 149(Pt 9);2427-33. PMID: 12949168

Stancek05: Stancek M, Schnell R, Ryden-Aulin M (2005). "Analysis of Escherichia coli nicotinate mononucleotide adenylyltransferase mutants in vivo and in vitro." BMC Biochem 6;16. PMID: 16153292

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

UniProtGOA12: UniProt-GOA (2012). "Gene Ontology annotation based on UniPathway vocabulary mapping."

Zhang02c: Zhang H, Zhou T, Kurnasov O, Cheek S, Grishin NV, Osterman A (2002). "Crystal structures of E. coli nicotinate mononucleotide adenylyltransferase and its complex with deamido-NAD." Structure (Camb) 10(1);69-79. PMID: 11796112

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by SRI International Pathway Tools version 19.0 on Fri Oct 9, 2015, biocyc12.