Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.5 (5'-nucleotidase)
 3,167 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Haemophilus influenzae has an absolute requirement for NAD (factor V) because it lacks almost all the biosynthetic enzymes necessary for the de novo synthesis of that cofactor. Factor V can be provided as either nicotinamide adenosine dinucleotide (NAD), nicotinamide mononucleotide (NMN), or nicotinamide riboside (NR) in vitro, but little is known about the source or the mechanism of uptake of these substrates in vivo. As shown by us earlier, at least two gene products are involved in the uptake of NAD, the outer membrane lipoprotein e (P4), which has phosphatase activity and is encoded by hel, and a periplasmic NAD nucleotidase, encoded by nadN. It has also been observed that the latter gene product is essential for H. influenzae growth on media supplemented with NAD. In this report, we describe the functions and substrates of these two proteins as they act together in an NAD utilization pathway. Data are provided which indicate that NadN harbors not only NAD pyrophosphatase but also NMN 5'-nucleotidase activity. The e (P4) protein is also shown to have NMN 5'-nucleotidase activity, recognizing NMN as a substrate and releasing NR as its product. Insertion mutants of nadN or deletion and site-directed mutants of hel had attenuated growth and a reduced uptake phenotype when NMN served as substrate. A hel and nadN double mutant was only able to grow in the presence of NR, whereas no uptake of NMN was observed.
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PMID:NadN and e (P4) are essential for utilization of NAD and nicotinamide mononucleotide but not nicotinamide riboside in Haemophilus influenzae. 1139 61

Haemophilus influenzae has an absolute requirement for factor V because it lacks all the biosynthetic enzymes necessary for the de novo synthesis of NAD. Factor V can be provided as either nicotinamide adenosine dinucleotide (NAD), nicotinamide mono-nucleotide (NMN) or nicotinamide riboside (NR) in vitro, but little is known about the source or the mechanism of uptake for factor V in vivo. Recently, a hypothetical open reading frame (ORF), termed nadN, was identified to encode a gene product essential for H. influenzae growth on NAD. Here, we report its role in the virulent H. influenzae serotype b strain Eagan. Our results indicate that NadN of type b Eagan strains is involved in NAD uptake and in processing NAD to NR, which appears to be the substrate for an as yet unidentified cytoplasmic membrane NR transport system. Furthermore, we present data showing that H. influenzae type b nadN mutants are able to survive as well as Eagan, in vivo in the five-day-old infant rat model of human invasive disease. NAD pyrophosphatase and NMN 5'-nucleotidase activities were present in rat and human serum, implying that under infection conditions H. influenzae may obtain NR directly from its host.
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PMID:Is a NAD pyrophosphatase activity necessary for Haemophilus influenzae type b multiplication in the blood stream? 1155 62