Department of Biochemistry and Molecular Biology, 985870 Nebraska Medical Center, Omaha, NE, USA.
Eppley Institute for Cancer and Allied Diseases, 986805 Nebraska Medical Center, Omaha, NE, USA.
Nat Commun. 2021 Apr 6;12(1):2079. doi: 10.1038/s41467-021-22290-1.
Human manganese superoxide dismutase is a critical oxidoreductase found in the mitochondrial matrix. Concerted proton and electron transfers are used by the enzyme to rid the mitochondria of O. The mechanisms of concerted transfer enzymes are typically unknown due to the difficulties in detecting the protonation states of specific residues and solvent molecules at particular redox states. Here, neutron diffraction of two redox-controlled manganese superoxide dismutase crystals reveal the all-atom structures of Mn and Mn enzyme forms. The structures deliver direct data on protonation changes between oxidation states of the metal. Observations include glutamine deprotonation, the involvement of tyrosine and histidine with altered pKs, and four unusual strong-short hydrogen bonds, including a low barrier hydrogen bond. We report a concerted proton and electron transfer mechanism for human manganese superoxide dismutase from the direct visualization of active site protons in Mn and Mn redox states.
人锰超氧化物歧化酶是一种存在于线粒体基质中的关键氧化还原酶。该酶利用协同质子和电子转移来清除线粒体中的 O。由于难以检测特定残基和溶剂分子在特定氧化还原状态下的质子化状态，协同转移酶的机制通常是未知的。在这里，两种氧化还原控制的锰超氧化物歧化酶晶体的中子衍射揭示了 Mn 和 Mn 酶形式的全原子结构。这些结构提供了关于金属氧化态之间质子化变化的直接数据。观察结果包括谷氨酰胺去质子化、酪氨酸和组氨酸与改变的 pKs 的参与，以及四个异常强的短氢键，包括一个低势垒氢键。我们从 Mn 和 Mn 氧化还原态中活性位点质子的直接可视化报告了人锰超氧化物歧化酶的协同质子和电子转移机制。
