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À propos de : Direct Detection of Hydrogen Bonds in Monomeric Superoxide Dismutase: Biological Implications        

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  • Direct Detection of Hydrogen Bonds in Monomeric Superoxide Dismutase: Biological Implications
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  • Hydrogen bonds were directly determined via NMR with different experimental approachesat 600 and 800 MHz for reduced monomeric superoxide dismutase (Q133M2SOD, 16 kDa). This proteincontains a copper and a zinc ion and shows the classical superoxide dismutase (SOD) eight-strandedβ-barrel fold. The best results for this intermediate molecular mass protein were obtained using a TROSYversion of the long-range HNCO experiment at high magnetic field (800 MHz) or with a cryoprobe at600 MHz. The backbone hydrogen bond network that defines the secondary structure of the protein wasdetected. Thirty-five backbone hydrogen bonds were identified. The lower limit for their detection, theirrelation to the TROSY R2 rates, and the correlation between hydrogen bond detectability and signal linewidth are discussed. Experiments were also optimized to detect hydrogen bonds involving key side chains,which lead to the observation of five hydrogen bonds. In particular, the hydrogen bonds involving theside chain of Asp 124 were observed, which show significant differences with respect to the bonds expectedon the basis of the crystal structure. The relevance of this finding relies also on the fact that Asp 124 isa key residue in determining the affinity of the protein for zinc. It has now been determined that the gainof the toxic function of peroxynitrite formation in SOD mutants related to amyotrophic lateral sclerosis(ALS) is due to SOD species lacking the zinc ion, as a consequence of a reduced affinity for zinc. Therefore,this study provides structural hints for understanding the origin of the enzymatic behavior of the Zn-deficient SOD.
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