IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-50260-w.html
   My bibliography  Save this article

Revealing the atomic and electronic mechanism of human manganese superoxide dismutase product inhibition

Author

Listed:
  • Jahaun Azadmanesh

    (Eppley Institute for Research in Cancer and Allied Diseases)

  • Katelyn Slobodnik

    (Eppley Institute for Research in Cancer and Allied Diseases)

  • Lucas R. Struble

    (Eppley Institute for Research in Cancer and Allied Diseases)

  • William E. Lutz

    (Eppley Institute for Research in Cancer and Allied Diseases)

  • Leighton Coates

    (Oak Ridge National Laboratory)

  • Kevin L. Weiss

    (Oak Ridge National Laboratory)

  • Dean A. A. Myles

    (Oak Ridge National Laboratory)

  • Thomas Kroll

    (SLAC National Accelerator Laboratory)

  • Gloria E. O. Borgstahl

    (Eppley Institute for Research in Cancer and Allied Diseases)

Abstract

Human manganese superoxide dismutase (MnSOD) is a crucial oxidoreductase that maintains the vitality of mitochondria by converting superoxide (O2●−) to molecular oxygen (O2) and hydrogen peroxide (H2O2) with proton-coupled electron transfers (PCETs). Human MnSOD has evolved to be highly product inhibited to limit the formation of H2O2, a freely diffusible oxidant and signaling molecule. The product-inhibited complex is thought to be composed of a peroxide (O22−) or hydroperoxide (HO2−) species bound to Mn ion and formed from an unknown PCET mechanism. PCET mechanisms of proteins are typically not known due to difficulties in detecting the protonation states of specific residues that coincide with the electronic state of the redox center. To shed light on the mechanism, we combine neutron diffraction and X-ray absorption spectroscopy of the product-bound, trivalent, and divalent states of the enzyme to reveal the positions of all the atoms, including hydrogen, and the electronic configuration of the metal ion. The data identifies the product-inhibited complex, and a PCET mechanism of inhibition is constructed.

Suggested Citation

  • Jahaun Azadmanesh & Katelyn Slobodnik & Lucas R. Struble & William E. Lutz & Leighton Coates & Kevin L. Weiss & Dean A. A. Myles & Thomas Kroll & Gloria E. O. Borgstahl, 2024. "Revealing the atomic and electronic mechanism of human manganese superoxide dismutase product inhibition," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50260-w
    DOI: 10.1038/s41467-024-50260-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-50260-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-50260-w?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Lukas Gajdos & Matthew P. Blakeley & Michael Haertlein & V. Trevor Forsyth & Juliette M. Devos & Anne Imberty, 2022. "Neutron crystallography reveals mechanisms used by Pseudomonas aeruginosa for host-cell binding," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    2. Steven Dajnowicz & Ryne C. Johnston & Jerry M. Parks & Matthew P. Blakeley & David A. Keen & Kevin L. Weiss & Oksana Gerlits & Andrey Kovalevsky & Timothy C. Mueser, 2017. "Direct visualization of critical hydrogen atoms in a pyridoxal 5′-phosphate enzyme," Nature Communications, Nature, vol. 8(1), pages 1-9, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Jody Pacalon & Guillaume Audic & Justine Magnat & Manon Philip & Jérôme Golebiowski & Christophe J. Moreau & Jérémie Topin, 2023. "Elucidation of the structural basis for ligand binding and translocation in conserved insect odorant receptor co-receptors," Nature Communications, Nature, vol. 14(1), pages 1-11, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50260-w. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.