The role of Tyr34 in proton coupled electron transfer and product inhibition of manganese superoxide dismutase

Jahaun Azadmanesh, Katelyn Slobodnik, Lucas R. Struble, Jeffrey J. Lovelace, Erika A. Cone, Medhanjali Dasgupta, William E. Lutz, Siddhartha Kumar, Amarnath Natarajan, Leighton Coates, Kevin L. Weiss, Dean A. A. Myles, Thomas Kroll and Gloria E. O. Borgstahl ()
Additional contact information
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
Jeffrey J. Lovelace: Eppley Institute for Research in Cancer and Allied Diseases
Erika A. Cone: Eppley Institute for Research in Cancer and Allied Diseases
Medhanjali Dasgupta: Eppley Institute for Research in Cancer and Allied Diseases
William E. Lutz: Eppley Institute for Research in Cancer and Allied Diseases
Siddhartha Kumar: Eppley Institute for Research in Cancer and Allied Diseases
Amarnath Natarajan: 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

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract Human manganese superoxide dismutase (MnSOD) plays a crucial role in controlling levels of reactive oxygen species (ROS) by converting superoxide ( $${{{{\rm{O}}}}}_{2}^{\bullet -}$$ O 2 ∙ − ) to molecular oxygen (O2) and hydrogen peroxide (H2O2) with proton-coupled electron transfers (PCETs). A key catalytic residue, Tyr34, determines the activity of human MnSOD and also becomes post-translationally inactivated by nitration in various diseases associated with mitochondrial dysfunction. Tyr34 has an unusual pKa due to its proximity to the Mn metal and undergoes cyclic deprotonation and protonation events to promote the electron transfers of MnSOD. Neutron diffraction, X-ray spectroscopy, and quantum chemistry calculations in oxidized, reduced and product inhibited enzymatic states shed light on the role of Tyr34 in MnSOD catalysis. The data identify the contributions of Tyr34 in MnSOD activity that support mitochondrial function and give a thorough characterization of how a single tyrosine modulates PCET catalysis. Product inhibition occurs by an associative displacement mechanism.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-57180-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57180-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-57180-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().