Selective oxidation of methionyl residues in the human recombinant secretory leukocyte proteinase inhibitor. Effect on the inhibitor binding properties

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Abstract
Binding of the human recombinant secretory leukocyte proteinase inhibitor (SLPI) [native and with the methionyl residues at positions 73, 82, 94 and 96 of domain 2 oxidized to the sulfoxide derivative (Met(O) SLPI)] to bovine α‐chymotrypsin (α‐chymotrypsin) [native and with the Met192 residue converted to the sufoxide derivative (Met(O) α‐chymotrypsin)] as well as to native bovine β‐trypsin (β‐trypsin), which does not contain methionyl residues, has been investigated between pH 4.0 and 8.0, and between 10.0°C ad 30.0°C, from thermodynamic and/or kinetic viewpoints. By increasing the number of oxidized methytonyl residues present at the proteinase: inhibitor contact interface (from 0 to 3), the adducts investigated are increasingly destabilized and the relaxation time of the complexes into conformers less stable is enhanced. On the other hand, the selective oxidation methionyl residues of SLPI and α‐chymotrypsin, by the reaction with chloramines T, does not affect the proteinase inhibition recognition mechanism. Therefore, even though conformational changes may occur in the conversion native SLPI and native α‐chymotrypsin to their Met(O) derivatives, a localized steric hindrance can be considered as the main structural determinant accounting for the reported results.