Document Detail

Structure and function of an ADP-ribose-dependent transcriptional regulator of NAD metabolism.
MedLine Citation:
PMID:  19604474     Owner:  NLM     Status:  MEDLINE    
Besides its function as an essential redox cofactor, nicotinamide adenine dinucleotide (NAD) also serves as a consumable substrate for several reactions with broad impact on many cellular processes. NAD homeostasis appears to be tightly controlled, but the mechanism of its regulation is little understood. Here we demonstrate that a previously predicted bacterial transcriptional regulator, NrtR, represses the transcription of NAD biosynthetic genes in vitro. The NAD metabolite ADP-ribose functions as an activator suppressing NrtR repressor activity. The presence of high ADP-ribose levels in the cell is indicative of active NAD turnover in bacteria, which could signal the activation of NAD biosynthetic gene expression via inhibiting the repressor function of NrtR. By comparing the crystal structures of NrtR in complex with DNA and with ADP-ribose, we identified a "Nudix switch" element that likely plays a critical role in the allosteric regulation of DNA binding and repressor function of NrtR.
Nian Huang; Jessica De Ingeniis; Luca Galeazzi; Chiara Mancini; Yuri D Korostelev; Alexandra B Rakhmaninova; Mikhail S Gelfand; Dmitry A Rodionov; Nadia Raffaelli; Hong Zhang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Structure (London, England : 1993)     Volume:  17     ISSN:  1878-4186     ISO Abbreviation:  Structure     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-07-16     Completed Date:  2009-12-07     Revised Date:  2014-09-10    
Medline Journal Info:
Nlm Unique ID:  101087697     Medline TA:  Structure     Country:  United States    
Other Details:
Languages:  eng     Pagination:  939-51     Citation Subset:  IM    
Data Bank Information
Bank Name/Acc. No.:
PDB/3GZ5;  3GZ6;  3GZ8
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MeSH Terms
Adenosine Diphosphate / metabolism,  physiology*
Adenosine Diphosphate Ribose / metabolism,  physiology*
Binding Sites
Crystallography, X-Ray
DNA, Fungal / isolation & purification,  metabolism
Hydrogen Bonding
Models, Molecular*
NAD / metabolism*
Protein Conformation
RNA, Fungal / isolation & purification,  metabolism
Saccharomyces / chemistry,  cytology,  growth & development
Sirtuins / metabolism,  physiology*
Templates, Genetic
Transcription, Genetic
Grant Support
55005610//Howard Hughes Medical Institute; AI059146/AI/NIAID NIH HHS; R01 AI059146/AI/NIAID NIH HHS; R01 AI059146-04/AI/NIAID NIH HHS
Reg. No./Substance:
0/DNA, Fungal; 0/RNA, Fungal; 0U46U6E8UK/NAD; 20762-30-5/Adenosine Diphosphate Ribose; 61D2G4IYVH/Adenosine Diphosphate; EC 3.5.1.-/Sirtuins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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