Transcriptional regulation of NAD metabolism in bacteria: NrtR family of Nudix-related regulators

Rodionov, Dmitry A.; De Ingeniis, Jessica; Mancini, Chiara; Cimadamore, Flavio; Zhang, Hong; Osterman, Andrei L.; Raffaelli, Nadia

doi:10.1093/nar/gkn047

Title: Transcriptional regulation of NAD metabolism in bacteria: NrtR family of Nudix-related regulators

Journal Article · Thu Feb 14 00:00:00 EST 2008 · Nucleic Acids Research

DOI:https://doi.org/10.1093/nar/gkn047· OSTI ID:1625439

Rodionov, Dmitry A. ^[1]; De Ingeniis, Jessica ^[2]; Mancini, Chiara ^[3]; Cimadamore, Flavio ^[4]; Zhang, Hong ^[5]; Osterman, Andrei L. ^[6]; Raffaelli, Nadia ^[3]

Burnham Inst. for Medical Research, La Jolla, CA (United States); Russian Academy of Sciences (RAS), Moscow (Russian Federation). Inst. for Information Transmission Problems
Universita Politecnica delle Marche, Ancona (Italy). Istituto di Biotecnologie Biochimiche
Universita Politecnica delle Marche, Ancona (Italy). Istituto di Biotecnologie Biochimiche
Burnham Inst. for Medical Research, La Jolla, CA (United States); Universita Politecnica delle Marche, Ancona (Italy). Istituto di Biotecnologie Biochimiche
Univ. of Texas Southwestern Medical Center, Dallas, TX (United States). Dept. of Biochemistry
Burnham Inst. for Medical Research, La Jolla, CA (United States); Fellowship for Interpretation of Genomes, Burr Ridge, IL (United States)

A novel family of transcription factors responsible for regulation of various aspects of NAD synthesis in a broad range of bacteria was identified by comparative genomics approach. Regulators of this family (here termed NrtR for Nudix-related transcriptional regulators), currently annotated as ADPribose pyrophosphatases from the Nudix family, are composed of an N-terminal Nudix-like effector domain and a C-terminal DNA-binding HTH-like domain. NrtR regulons were reconstructed in diverse bacterial genomes by identification and comparative analysis of NrtR-binding sites upstream of genes involved in NAD biosynthetic pathways. The candidate NrtR-binding DNA motifs showed significant variability between microbial lineages, although the common consensus sequence could be traced for most of them. Bioinformatics predictions were experimentally validated by gel mobility shift assays for two NrtR family representatives. ADP-ribose, the product of glycohydrolytic cleavage of NAD, was found to suppress the in vitro binding of NrtR proteins to their DNA target sites. In addition to a major role in the direct regulation of NAD homeostasis, some members of NrtR family appear to have been recruited for the regulation of other metabolic pathways, including sugar pentoses utilization and biogenesis of phosphoribosyl pyrophosphate. This work and the accompanying study of NiaR regulon demonstrate significant variability of regulatory strategies for control of NAD metabolic pathway in bacteria.

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Research Organization:: Burnham Institute for Medical Research, La Jolla, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division; National Institutes of Health (NIH)

Grant/Contract Number:: FG02-07ER64384; 1-R01-AI066244-01A2

OSTI ID:: 1625439

Journal Information:: Nucleic Acids Research, Vol. 36, Issue 6; ISSN 0305-1048

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United States

Language:: English

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