Significance of Knotted Structures for Function of Proteins and Nucleic Acids
Poster Session I
23 – POS
Board 23
The Iron-oxygen Switch in Anaerobic Bacterium Porphyromonas Gingivalis
Janina Lewis
, Cecilia Anaya - Bergman, Sai Yanamandra.
Virginia Commonwealth University, Richmond, USA.
Bacterial regulation of oxidative stress response typically includes proteins like SoxRS, PerR and
OxyR, while iron uptake mechanisms are regulated by iron-dependent regulators like Fur or
DtxR-like proteins. Here we investigated the iron-dependent transcriptome of the anaerobic
bacterium Porphyromonas gingivalis. We show that the bacterium regulates both iron uptake and
oxidative stress mechanisms utilizing a homolog of the nitrate/peroxide stress regulator OxyR.
We present the structure of the protein determined using x-ray crystallography. Transcriptional
profiling reveals that the mode of regulation by OxyR is dependent on iron levels present in cell
culture. We show that this OxyR protein binds iron, which we hypothesize coordinates the ligand
in the redox cysteine 199 (Cys199) site analogous to that of Escherichia coli and Neisseria
meningitides OxyR. A Cys199Ser mutation abolishes protein binding to iron as well as DNA and
confers a bacterial phenotype like the OxyR deficient strain. Our data support a new mode of
OxyR activation in the anaerobe P. gingivalis that depends on iron binding and leads to
regulation of both iron uptake and oxidative stress response genes. Based on structural similarity
of P. gingivalis and E. coli OxyR’s our model may also shed light on previous modes of OxyR
regulation in aerobic bacteria, which involve an oxidative stress induced cysteine switch or
cysteine nitrosylation, as such modifications may be metal-catalyzed thus allowing for sensing
low levels of peroxide or nitrite in vivo.
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