The reported human NADsyn2 is ammonia-dependent NAD synthetase from a pseudomonad

Pawel Bieganowski; Charles Brenner

doi:10.1074/jbc.M302276200

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The reported human NADsyn2 is ammonia-dependent NAD synthetase from a pseudomonad

Journal article

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The reported human NADsyn2 is ammonia-dependent NAD synthetase from a pseudomonad

Pawel Bieganowski and Charles Brenner

The Journal of biological chemistry, Vol.278(35), pp.33056-33059

08/29/2003

DOI: 10.1074/jbc.M302276200

PMID: 12777395

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Abstract

Nicotinamide-adenine dinucleotide (NAD+) synthetases catalyze the last step in NAD+ metabolism in the de novo, import, and salvage pathways that originate from tryptophan (or aspartic acid), nicotinic acid, and nicotinamide, respectively, and converge on nicotinic acid mononucleotide. NAD+ synthetase converts nicotinic acid adenine dinucleotide to NAD+ via an adenylylated intermediate. All of the known eukaryotic NAD+ synthetases are glutamine-dependent, hydrolyzing glutamine to glutamic acid to provide the attacking ammonia. In the prokaryotic world, some NAD+ synthetases are glutamine-dependent, whereas others can only use ammonia. Earlier, we noted a perfect correlation between presence of a domain related to nitrilase and glutamine dependence and then proved in the accompanying paper (Bieganowski, P., Pace, H. C., and Brenner, C. (2003) J. Biol. Chem. 278, 33049-33055) that the nitrilase-related domain is an essential, obligate intramolecular, thiol-dependent glutamine amidotransferase in the yeast NAD+ synthetase, Qns1. Independently, human NAD+ synthetase was cloned and shown to depend on Cys-175 for glutamine-dependent but not ammonia-dependent NAD+ synthetase activity. Additionally, it was claimed that a 275 amino acid open reading frame putatively amplified from human glioma cell line LN229 encodes a human ammonia-dependent NAD+ synthetase and this was speculated largely to mediate NAD+ synthesis in human muscle tissues. Here we establish that the so-called NADsyn2 is simply ammonia-dependent NAD+ synthetase from Pseudomonas, which is encoded on an operon with nicotinic acid phosphoribosyltransferase and, in some Pseudomonads, with nicotinamidase.

Protein Structure, Tertiary

Chromosomes, Human, Pair 22 - metabolism

Gene Library

Nicotinamidase - metabolism

Operon

Humans

Open Reading Frames

Molecular Sequence Data

Cysteine - chemistry

DNA - metabolism

Phylogeny

Amide Synthases - chemistry

Sequence Homology, Nucleic Acid

Hydrolysis

NAD - chemistry

Base Sequence

Cloning, Molecular

CpG Islands

Glutamine - chemistry

Amide Synthases - genetics

Ammonia - chemistry

Muscles - metabolism

Pseudomonas - metabolism

Glutamic Acid - chemistry

Details

Title: Subtitle: The reported human NADsyn2 is ammonia-dependent NAD synthetase from a pseudomonad
Creators: Pawel Bieganowski - Structural Biology and Bioinformatics Program, Kimmel Cancer Center, Philadelphia, Pennsylvania 19107, USA
Charles Brenner
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.278(35), pp.33056-33059
DOI: 10.1074/jbc.M302276200
PMID: 12777395
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: CA77738 / NCI NIH HHS P01 CA077738-040003 / NCI NIH HHS P01 CA077738 / NCI NIH HHS
Language: English
Date published: 08/29/2003
Academic Unit: Biochemistry and Molecular Biology; Internal Medicine
Record Identifier: 9983788599102771

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