Different selectivities of oxidants during oxidation of methionine residues in the α‐1‐proteinase inhibitor

FEBS Letters

Matejkova, Eva¹  Hinze, Helga¹  Beck-Speier, Ingrid¹  Leuschel, Lieselotte¹  Maier, Konrad L.¹  Weber, Hans¹ 

[1]GSF - Projekt Inhalation, Arbeitsgruppe Biochemie, D-8042 Neuherberg, FRG

关键词: Proteinase inhibitor;    α-1-;    Methionine;    Methionine sulfoxide;    Myeloperoxidase;    Xanthine oxidase;    Ozone;    Chloroperoxybenzoic acid;    m-;    Sulfite;    Met;    methionine;    Met(O);    methionine sulfoxide;    α-1-PI;    α-1-proteinase inhibitor;   

DOI  :  10.1016/0014-5793(89)80725-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Oxidation of the reactive site methionine (Met) in α-1-proteinase inhibitor (α-1-PI) to methionine sulfoxide (Met(O)) is known to cause depletion of its elastase inhibitory activity. To estimate the selectivity of different oxidants in converting Met to Met(O) in α-1-PI, we measured the molar ratio Met(O)/α-1-PI at total inactivation. This ratio was determined to be 1.2 for both the myeloperoxidase/H₂O₂/chloride system and the related compound NH₂Cl. With taurine monochloramine, another myeloperoxidase-related oxidant, 1.05 mol Met(O) were generated per mol α-1-PI during inactivation. These oxidants attack preferentially one Met residue in α-1-PI, which is identical with Met 358, as concluded from the parallelism of loss of elastase inhibitory activity and oxidation of Met. A similar high specificity for Met oxidation was determined for the xanthine oxidase-derived oxidants. In contrast, the ratio found for ozone and m-chloroperoxybenzoic acid was 6.0 and 5.0, respectively, indicating oxidation of additional Met residues besides the reactive site Met in α-1-PI, i.e. unselective action of these oxidants. Further studies were performed on the efficiency of oxidants for total depletion of the elastase inhibitory capacity of α-1-PI. Ozone and m-chloroperoxybenzoic acid were 10-fold less effective and the superoxide anion/hydroxyl radicals were 30–50-fold less effective to inactivate the elastase inhibitory activity as compared to the myeloperoxidase-derived oxidants. The myeloperoxidase-related oxidants are discussed as important regulators of α-1-PI activity in vivo.

【 授权许可】

Unknown