|Gene:||nadD||Accession Numbers: G6350 (EcoCyc), b0639, ECK0632|
Synonyms: ybeN, fusB
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 [Zhang02a].
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].
|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
|Biological Process:||GO:0034355 - NAD salvage
GO:0034628 - 'de novo' NAD biosynthetic process from aspartate [Stancek03]
GO:0009058 - biosynthetic process [GOA01]
GO:0009435 - NAD biosynthetic process [UniProtGOA12, GOA06, GOA01]
GO:0019363 - pyridine nucleotide biosynthetic process [UniProtGOA11]
|Molecular Function:||GO:0004515 - nicotinate-nucleotide adenylyltransferase activity
[GOA06, GOA01a, Mehl00]
GO:0000166 - nucleotide binding [UniProtGOA11]
GO:0003824 - catalytic activity [GOA01]
GO:0005524 - ATP binding [UniProtGOA11]
GO:0016740 - transferase activity [UniProtGOA11]
GO:0016779 - nucleotidyltransferase activity [UniProtGOA11, GOA01]
|Cellular Component:||GO:0005829 - cytosol [DiazMejia09]|
|MultiFun Terms:||metabolism → biosynthesis of building blocks → cofactors, small molecule carriers → nicotinamide adenine dinucleotide|
|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]|
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: 184.108.40.206
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.
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.
pH(opt): 7.5 [Imsande61]
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
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
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
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
Zhang02a: 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
©2014 SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025-3493