8VJ4

X-ray Counterpart to the Neutron Structure of Peroxide-Soaked Trp161Phe MnSOD

8VJ4 の概要

• エントリーDOI: 10.2210/pdb8vj4/pdb
• 分子名称: Superoxide dismutase [Mn], mitochondrial, MANGANESE (II) ION, HYDROGEN PEROXIDE, ... (4 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: 44828.45

構造登録者

Azadmanesh, J.,Slobodnik, K.,Struble, L.R.,Lutz, W.E.,Weiss, K.L.,Myles, D.A.A.,Kroll, T.,Borgstahl, G.E.O. (登録日: 2024-01-05, 公開日: 2024-07-31, 最終更新日: 2024-10-16)

主引用文献

Azadmanesh, J.,Slobodnik, K.,Struble, L.R.,Lutz, W.E.,Coates, L.,Weiss, K.L.,Myles, D.A.A.,Kroll, T.,Borgstahl, G.E.O.
Revealing the atomic and electronic mechanism of human manganese superoxide dismutase product inhibition.
Nat Commun, 15:5973-5973, 2024

PubMed Abstract: Human manganese superoxide dismutase (MnSOD) is a crucial oxidoreductase that maintains the vitality of mitochondria by converting superoxide (O) to molecular oxygen (O) and hydrogen peroxide (HO) with proton-coupled electron transfers (PCETs). Human MnSOD has evolved to be highly product inhibited to limit the formation of HO, a freely diffusible oxidant and signaling molecule. The product-inhibited complex is thought to be composed of a peroxide (O) or hydroperoxide (HO) 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.

PubMed: 39013847
DOI: 10.1038/s41467-024-50260-w

実験手法

X-RAY DIFFRACTION (1.68 Å)