9BW2

Neutron Structure of Reduced Tyr34Phe MnSOD

9BW2 の概要

• エントリーDOI: 10.2210/pdb9bw2/pdb
• 関連するPDBエントリー: 9BVY
• 分子名称: Superoxide dismutase [Mn], mitochondrial, MANGANESE (II) ION (3 entities in total)
• 機能のキーワード: oxidoreductase, mnsod, sod2, pcet
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 44806.49

構造登録者

Azadmanesh, J.,Slobodnik, K.,Struble, L.R.,Cone, E.A.,Dasgupta, M.,Lutz, W.E.,Kumar, S.,Natarajan, A.,Coates, L.,Weiss, K.L.,Myles, D.A.A.,Kroll, T.,Borgstahl, G.E.O. (登録日: 2024-05-20, 公開日: 2025-03-12)

主引用文献

Azadmanesh, J.,Slobodnik, K.,Struble, L.R.,Lovelace, J.J.,Cone, E.A.,Dasgupta, M.,Lutz, W.E.,Kumar, S.,Natarajan, A.,Coates, L.,Weiss, K.L.,Myles, D.A.A.,Kroll, T.,Borgstahl, G.E.O.
The role of Tyr34 in proton coupled electron transfer and product inhibition of manganese superoxide dismutase.
Nat Commun, 16:1887-1887, 2025

PubMed Abstract: Human manganese superoxide dismutase (MnSOD) plays a crucial role in controlling levels of reactive oxygen species (ROS) by converting superoxide ( ) to molecular oxygen (O) and hydrogen peroxide (HO) 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 pK 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.

PubMed: 39987263
DOI: 10.1038/s41467-025-57180-3

実験手法

NEUTRON DIFFRACTION (2.5 Å)