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MedLine Citation:
PMID:  22424265     Owner:  NLM     Status:  Publisher    
Aims. In the opportunistic pathogen Pseudomonas aeruginosa nitric oxide (NO) triggers the respiration of nitrate (denitrification) thus allowing survival in chronic infection sites as a microaerobic-anaerobic biofilm. The NO-dependent induction of denitrification is mediated by the DNR, a transcription factor forming a stable complex with heme, which is required to sense the physiological messenger (i.e. NO). The molecular details of NO-sensing in DNR and, more in general, in this class of sensors are largely unknown and a study aimed at integrating microbiology and biochemistry is needed. Results. Here we present a comprehensive study, including in vivo results and spectroscopy, kinetics and protein engineering, that demonstrates the direct involvement of an histidine residue in heme iron coordination. Moreover, a peculiar phenomenon of ligand switching around heme iron, which hampers the identification of the second heme axial ligand, is also suggested. These results indicate that DNR is characterized by a remarkable flexibility in solution, as observed for other CRP-FNR regulators to which DNR belongs. Innovation. The present work represents one of the few studies focused on the biochemistry of NO sensing by bacterial transcriptional regulators. The data presented demonstrate that structural plasticity of DNR is crucial for the sensing activity and confers to the protein unusual heme binding properties. Conclusions. Protein flexibility and dynamics is a key structural feature essential to explain the evolutionary success and adaptability of CRP-FNR regulators, and may represent a common strategy employed by heme-based redox sensors, which presents features deeply different from those of "canonical" hemeproteins.
Serena Rinaldo; Nicoletta Castiglione; Giorgio Giardina; Manuela Caruso; Alessandro Arcovito; Stefano Della Longa; Paola D'Angelo; Francesca Cutruzzolà
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-18
Journal Detail:
Title:  Antioxidants & redox signaling     Volume:  -     ISSN:  1557-7716     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-3-19     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100888899     Medline TA:  Antioxid Redox Signal     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Istituto Pasteur-Fondazione Cenci Bolognetti, Rome, Italy;
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