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@ARTICLE{Sushko:904321,
author = {Sushko, Tatsiana and Kavaleuski, Anton and Grabovec, Irina
and Kavaleuskaya, Anna and Vakhrameev, Daniil and
Bukhdruker, Sergey and Marin, Egor and Kuzikov, Alexey and
Shumyantseva, Victoria and Masamrekh, Rami and Tsumoto,
Kouhei and Borshchevskiy, Valentin and Strushkevich,
Natallia and Gilep, Andrei},
title = {{A} new twist of rubredoxin function in {M}. tuberculosis},
journal = {Bioorganic chemistry},
volume = {109},
issn = {0045-2068},
address = {San Diego, Calif.},
publisher = {Elsevier},
reportid = {FZJ-2021-05891},
pages = {104721 -},
year = {2021},
abstract = {Electron transfer mediated by metalloproteins drives many
biological processes. Rubredoxins are a ubiquitous [1Fe-0S]
class of electron carriers that play an important role in
bacterial adaptation to changing environmental conditions.
In Mycobacterium tuberculosis, oxidative and acidic stresses
as well as iron starvation induce rubredoxins expression.
However, their functions during M. tuberculosis infection
are unknown. In the present work, we show that rubredoxin B
(RubB) is able to efficiently shuttle electrons from cognate
reductases, FprA and FdR to support catalytic activity of
cytochrome P450s, CYP124, CYP125, and CYP142, which are
important for bacterial viability and pathogenicity. We
solved the crystal structure of RubB and characterized the
interaction between RubB and CYPs using site-directed
mutagenesis. Mutations that not only neutralize single
charge but also change the specific residues on the surface
of RubB did not dramatically decrease activity of studied
CYPs. Together with isothermal calorimetry (ITC)
experiments, the obtained results suggest that interactions
are transient and not highly specific. The redox potential
of RubB is −264 mV vs. Ag/AgCl and the measured extinction
coefficients are 9931 M−1cm−1 and 8371 M−1cm−1 at
380 nm and 490 nm, respectively. Characteristic parameters
of RubB along with the discovered function might be useful
for biotechnological applications. Our findings suggest that
a switch from ferredoxins to rubredoxins might be crucial
for M. tuberculosis to support CYPs activity during the
infection.},
cin = {IBI-7},
ddc = {540},
cid = {I:(DE-Juel1)IBI-7-20200312},
pnm = {5241 - Molecular Information Processing in Cellular Systems
(POF4-524)},
pid = {G:(DE-HGF)POF4-5241},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:33618255},
UT = {WOS:000636139600003},
doi = {10.1016/j.bioorg.2021.104721},
url = {https://juser.fz-juelich.de/record/904321},
}