Nicotinamide ribonucleoside uptake transporters
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| Identifiers | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Symbol | PnuC | ||||||||
| Pfam | PF04973 | ||||||||
| TCDB | 4.B.1 | ||||||||
| OPM superfamily | 377 | ||||||||
| OPM protein | 4qtn | ||||||||
| |||||||||
The Nicotinamide Ribonucleoside (NR) Uptake Permease (PnuC) Family (TC# 4.B.1) is a family of transmembrane transporters that is part of the TOG superfamily.[1] Close PnuC homologues are found in a wide range of Gram-negative and Gram-positive bacteria, archaea and eukaryotes.[2]
PnuC of Haemophilus influenzae
PnuC of Salmonella typhimurium and Haemophilus influenzae are believed to function cooperatively with NadR homologues, multifunctional proteins that together with PnuC, participate in NR phosphorylation, transport and transcriptional regulation.[3][4][5] NadR, a cytoplasmic protein that is partly membrane associated, contains one well conserved and one poorly conserved mononucleotide-binding consensus sequence (G-X4 GKS). It drives transport and may render transport responsive to internal pyridine nucleotide levels. While its N-terminal half functions as a repressor, its C-terminal half functions as an NR kinase in a putative group translocation process.[6]
The H. influenzae homologue has been shown to transport NR from the periplasm into the cytoplasm. Phosphorylation of NR by NadR is required for NR uptake. The ribonucleoside kinase (RNK) domain has both Walker A and Walker B motifs, responsible for ATP binding and phosphoryl transfer. In addition, a proposed LID domain was identified in RNK. LID domains have been found in other kinases, and these domains are regions which are able to move after substrate binding. They are responsible for coordination of three distinct conformations, an open state in the absence of substrate, a partially closed state after substrate binding, and a fully closed state when both substrates are present.
In H. influenzae, NR enters the NAD+ resynthesis pathway after phosphorylation to NMN, and subsequently, NAD+ is synthesized from NMN and ATP via an NMN adenylyl transferase activity.[7][8] NadR represents a multifunctional regulator/enzyme complex able to integrate several functions, such as enzymatic catalysis, transport, and transcriptional regulatory activities.
