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@ARTICLE{Wensien:459162,
      author       = {Wensien, Marie and von Pappenheim, Fabian Rabe and Funk,
                      Lisa-Marie and Kloskowski, Patrick and Curth, Ute and
                      Diederichsen, Ulf and Uranga, Jon and Ye, Jin and Fang, Pan
                      and Pan, Kuan-Ting and Urlaub, Henning and Mata, Ricardo A.
                      and Sautner, Viktor and Tittmann, Kai},
      title        = {{A} lysine–cysteine redox switch with an {NOS} bridge
                      regulates enzyme function},
      journal      = {Nature},
      volume       = {593},
      number       = {7859},
      issn         = {0028-0836},
      address      = {London [u.a.]},
      publisher    = {Nature Publ. Group},
      reportid     = {PUBDB-2021-02447},
      pages        = {460 - 464},
      year         = {2021},
      note         = {Copyright © 2021, The Author(s), under exclusive licence
                      to Springer Nature Limited},
      abstract     = {Disulfide bonds between cysteine residues are important
                      post-translational modifications in proteins that have
                      critical roles for protein structure and stability, as
                      redox-active catalytic groups in enzymes or allosteric redox
                      switches that govern protein function1,2,3,4. In addition to
                      forming disulfide bridges, cysteine residues are susceptible
                      to oxidation by reactive oxygen species, and are thus
                      central not only to the scavenging of these but also to
                      cellular signalling and communication in biological as well
                      as pathological contexts5,6. Oxidized cysteine species are
                      highly reactive and may form covalent conjugates with, for
                      example, tyrosines in the active sites of some redox
                      enzymes7,8. However, to our knowledge, regulatory switches
                      with covalent crosslinks other than disulfides have not
                      previously been demonstrated. Here we report the discovery
                      of a covalent crosslink between a cysteine and a lysine
                      residue with a NOS bridge that serves as an allosteric redox
                      switch in the transaldolase enzyme of Neisseria gonorrhoeae,
                      the pathogen that causes gonorrhoea. X-ray structure
                      analysis of the protein in the oxidized and reduced state
                      reveals a loaded-spring mechanism that involves a structural
                      relaxation upon redox activation, which is propagated from
                      the allosteric redox switch at the protein surface to the
                      active site in the protein interior. This relaxation leads
                      to a reconfiguration of key catalytic residues and elicits
                      an increase in enzymatic activity of several orders of
                      magnitude. The redox switch is highly conserved in related
                      transaldolases from other members of the Neisseriaceae; for
                      example, it is present in the transaldolase of Neisseria
                      meningitides (a pathogen that is the primary cause of
                      meningitis and septicaemia in children). We surveyed the
                      Protein Data Bank and found that the NOS bridge exists in
                      diverse protein families across all domains of life
                      (including Homo sapiens) and that it is often located at
                      catalytic or regulatory hotspots. Our findings will inform
                      strategies for the design of proteins and peptides, as well
                      as the development of new classes of drugs and antibodies
                      that target the lysine–cysteine redox switch.},
      cin          = {EMBL-User},
      ddc          = {500},
      cid          = {I:(DE-H253)EMBL-User-20120814},
      pnm          = {6G3 - PETRA III (DESY) (POF4-6G3)},
      pid          = {G:(DE-HGF)POF4-6G3},
      experiment   = {EXP:(DE-H253)P-P14-20150101},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33953398},
      UT           = {WOS:000647555000003},
      doi          = {10.1038/s41586-021-03513-3},
      url          = {https://bib-pubdb1.desy.de/record/459162},
}