Redox manipulation of the manganese metal in human manganese superoxide dismutase for neutron diffraction

Azadmanesh, Jahaun; Lutz, William E.; Weiss, Kevin L.; Coates, Leighton; Borgstahl, Gloria E. O.

doi:10.1107/s2053230x18011299

Cited by 14 publications

(17 citation statements)

References 62 publications

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“…The mitochondrion is the major site for ROS production and leakage [111,112]. Moderate ROS levels are essential for cell proliferation and survival by mitophagy [113,114].…”

Section: Mitophagymentioning

confidence: 99%

The Role of Reactive Oxygen Species in Arsenic Toxicity

et al. 2020

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Arsenic poisoning is a global health problem. Chronic exposure to arsenic has been associated with the development of a wide range of diseases and health problems in humans. Arsenic exposure induces the generation of intracellular reactive oxygen species (ROS), which mediate multiple changes to cell behavior by altering signaling pathways and epigenetic modifications, or cause direct oxidative damage to molecules. Antioxidants with the potential to reduce ROS levels have been shown to ameliorate arsenic-induced lesions. However, emerging evidence suggests that constructive activation of antioxidative pathways and decreased ROS levels contribute to chronic arsenic toxicity in some cases. This review details the pathways involved in arsenic-induced redox imbalance, as well as current studies on prophylaxis and treatment strategies using antioxidants.

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“…The mitochondrion is the major site for ROS production and leakage [111,112]. Moderate ROS levels are essential for cell proliferation and survival by mitophagy [113,114].…”

Section: Mitophagymentioning

confidence: 99%

The Role of Reactive Oxygen Species in Arsenic Toxicity

et al. 2020

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“…Redox manipulation of perdeuterated MnSOD crystals. Methods for manipulating the Mn metal of MnSOD to either Mn 3+ or Mn 2+ have been described previously 14 . In brief, a crystal in a quartz capillary was soaked in deuterated reservoir solutions containing either 6.4 mM potassium permanganate (KMnO4) to achieve the Mn 3+ state or 300 mM sodium hydrosulfite (Na2S2O4) to achieve the Mn 2+ state.…”

Section: Methodsmentioning

confidence: 99%

“…A KMnO4-treated perdeuterated crystal of 0.46 mm 3 in volume at 296K was recorded to 2.20 Å resolution for the Mn 3+ SOD form and subsequently treated with Na2S2O4 to achieve the Mn 2+ SOD state where 2.30 Å data were collected (Table S5). Na2S2O4 is noted to deteriorate diffraction quality and was observed to increase the c unit cell axis by ~1 Å 14 . After neutron data were collected from the crystal in the Mn 2+ SOD state, X-ray diffraction data were collected at 296 K to 2.16 Å resolution using a Rigaku FR-E SuperBright home source.…”

Section: Methodsmentioning

confidence: 99%

Direct detection of coupled proton and electron transfers in human manganese superoxide dismutase

Azadmanesh

Lutz

Coates

et al. 2020

Preprint

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Human manganese superoxide dismutase (MnSOD) is a critical oxidoreductase found in the mitochondrial matrix. Concerted proton and electron transfers (CPETs) are used by the enzyme to rid the mitochondria of O2•−, a precursor to other harmful reactive oxygen and nitrogen species. The mechanisms of CPET-utilizing enzymes are typically unknown due to the difficulties in detecting the protonation states of specific residues and solvent molecules involved in catalysis while controlling the redox state of the enzyme. Here, neutron diffraction of redox-controlled MnSOD crystals revealed the all-atom structures of Mn3+SOD and Mn2+SOD delivering unique data on sites of differential protonation. A novel mechanism is proposed from the direct observation of glutamine deprotonation, the involvement of Tyr and His with altered pKas, and three unusual strong-short hydrogen bonds that change with the oxidation state of the metal. Quantum calculations provide insight into the electronic modulation of the observed structures.

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“…The second is to obtain neutron diffraction data for GatCAB without overlap of Bragg peaks, because the unit cell of GatCAB is relatively large for neutron single-crystal diffractometers (Blakeley, 2009). Recently, Azadmenesh and coworkers reported the successful collection of time-of-flight (TOF) neutron diffraction data from a crystal with the largest unit-cell edge to date (240 Å ) using the MaNDi instrument at the Spallation Neutron Source (Azadmanesh et al, 2017(Azadmanesh et al, , 2018.…”

Section: Introductionmentioning

confidence: 99%

Neutron crystallographic study of heterotrimeric glutamine amidotransferase CAB

Adachi

et al. 2019

Acta Crystallogr F Struct Biol Commun

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Heterotrimeric glutamine amidotransferase CAB (GatCAB) possesses an ammonia‐self‐sufficient mechanism in which ammonia is produced and used in the inner complex by GatA and GatB, respectively. The X‐ray structure of GatCAB revealed that the two identified active sites of GatA and GatB are markedly distant, but are connected in the complex by a channel of 30 Å in length. In order to clarify whether ammonia is transferred through this channel in GatCAB by visualizing ammonia, neutron diffraction studies are indispensable. Here, GatCAB crystals were grown to approximate dimensions of 2.8 × 0.8 × 0.8 mm (a volume of 1.8 mm3) with the aid of a polymer using microseeding and macroseeding processes. Monochromatic neutron diffraction data were collected using the neutron single‐crystal diffractometer BIODIFF at the Heinz Maier‐Leibnitz Zentrum, Germany. The GatCAB crystals belonged to space group P212121, with unit‐cell parameters a = 74.6, b = 94.5, c = 182.5 Å and with one GatCAB complex (molecular mass 119 kDa) in the asymmetric unit. This study represented a challenge in current neutron diffraction technology.

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Redox manipulation of the manganese metal in human manganese superoxide dismutase for neutron diffraction

Cited by 14 publications

References 62 publications

The Role of Reactive Oxygen Species in Arsenic Toxicity

The Role of Reactive Oxygen Species in Arsenic Toxicity

Direct detection of coupled proton and electron transfers in human manganese superoxide dismutase

Neutron crystallographic study of heterotrimeric glutamine amidotransferase CAB

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