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@ARTICLE{Varaksa:904319,
      author       = {Varaksa, Tatsiana and Bukhdruker, Sergey and Grabovec,
                      Irina and Marin, Egor and Kavaleuski, Anton and Gusach,
                      Anastasiia and Kovalev, Kirill and Maslov, Ivan and
                      Luginina, Aleksandra and Zabelskii, Dmitrii and Astashkin,
                      Roman and Shevtsov, Mikhail and Smolskaya, Sviatlana and
                      Kavaleuskaya, Anna and Shabunya, Polina and Baranovsky,
                      Alexander and Dolgopalets, Vladimir and Charnou, Yury and
                      Savachka, Aleh and Litvinovskaya, Raisa and Hurski, Alaksiej
                      and Shevchenko, Evgeny and Rogachev, Andrey and Mishin,
                      Alexey and Gordeliy, Valentin and Gabrielian, Andrei and
                      Hurt, Darrell E. and Nikonenko, Boris and Majorov,
                      Konstantin and Apt, Alexander and Rosenthal, Alex and Gilep,
                      Andrei and Borshchevskiy, Valentin and Strushkevich,
                      Natallia},
      title        = {{M}etabolic {F}ate of {H}uman {I}mmunoactive {S}terols in
                      {M}ycobacterium tuberculosis},
      journal      = {Journal of molecular biology},
      volume       = {433},
      number       = {4},
      issn         = {0022-2836},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier},
      reportid     = {FZJ-2021-05889},
      pages        = {166763 -},
      year         = {2021},
      abstract     = {Mycobacterium tuberculosis (Mtb) infection is among top ten
                      causes of death worldwide, and the number of drug-resistant
                      strains is increasing. The direct interception of human
                      immune signaling molecules by Mtb remains elusive, limiting
                      drug discovery. Oxysterols and secosteroids regulate both
                      innate and adaptive immune responses. Here we report a
                      functional, structural, and bioinformatics study of Mtb
                      enzymes initiating cholesterol catabolism and demonstrated
                      their interrelation with human immunity. We show that these
                      enzymes metabolize human immune oxysterol messengers. Rv2266
                      – the most potent among them – can also metabolize
                      vitamin D3 (VD3) derivatives. High-resolution structures
                      show common patterns of sterols binding and reveal a site
                      for oxidative attack during catalysis. Finally, we designed
                      a compound that binds and inhibits three studied proteins.
                      The compound shows activity against Mtb H37Rv residing in
                      macrophages. Our findings contribute to molecular
                      understanding of suppression of immunity and suggest that
                      Mtb has its own transformation system resembling the human
                      phase I drug-metabolizing system.},
      cin          = {IBI-7},
      ddc          = {610},
      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:33359098},
      UT           = {WOS:000616181400002},
      doi          = {10.1016/j.jmb.2020.166763},
      url          = {https://juser.fz-juelich.de/record/904319},
}