7klb
From Proteopedia
X-ray Counterpart to Neutron Structure of Reduced Human MnSOD
Structural highlights
DiseaseSODM_HUMAN Genetic variation in SOD2 is associated with susceptibility to microvascular complications of diabetes type 6 (MVCD6) [MIM:612634. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. FunctionSODM_HUMAN Destroys superoxide anion radicals which are normally produced within the cells and which are toxic to biological systems.[1] Publication Abstract from PubMedHuman 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 O2(*-). 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(3+) and Mn(2+) 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 pKas, 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(3+) and Mn(2+) redox states. Direct detection of coupled proton and electron transfers in human manganese superoxide dismutase.,Azadmanesh J, Lutz WE, Coates L, Weiss KL, Borgstahl GEO Nat Commun. 2021 Apr 6;12(1):2079. doi: 10.1038/s41467-021-22290-1. PMID:33824320[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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