Ceruloplasmin and myeloperoxidase in complex affect the enzymatic properties of each other

Abstract

Ceruloplasmin (CP), the multicopper oxidase of plasma, interacts with myeloperoxidase (MPO), an enzyme of leukocytes, and inhibits its peroxidase and chlorinating activity. Studies on the enzymatic properties shows that CP behaves as a competitive inhibitor impeding the binding of aromatic substrates to the active centre of MPO. The contact between CP and MPO probably entails conformational changes close to the p-phenylenediamine binding site in CP, which explains the observed activation by MPO of the substrate's oxidation. CP subjected to partial proteolysis was virtually unable to inhibit activity of MPO. The possible protein-protein interface is comprised of the area near active site of MPO and the loop linking domains 5 and 6 in CP. One of the outcomes of this study is the finding of a new link between antioxidant properties of CP and its susceptibility to proteolysis.

Ceruloplasmin Is an Endogenous Inhibitor of Myeloperoxidase

“…Ceruloplasmin was also shown to inhibit the peroxidase activity of myeloperoxidase (20,22), but there were inconsistencies in the extent of inhibition, with values for inhibition ranging from 40 to 70%. The degree of inhibition also increased with increasing size of the peroxidase substrate (25). This suggested that binding of ceruloplasmin to myeloperoxidase hinders large substrates from accessing the active site of the enzyme.…”

“…In subsequent studies, it was found to be a modest inhibitor of the halogenation activity of myeloperoxidase (24,25). Ceruloplasmin was also shown to inhibit the peroxidase activity of myeloperoxidase (20,22), but there were inconsistencies in the extent of inhibition, with values for inhibition ranging from 40 to 70%.…”

Rapid insight into C60 influence on biological functions of proteins

“…There are many amino acid residues involved in interactions with fullerene C 60 on ceruloplasmin surface, which are considered as crucial for ceruloplasmin-lactoferrin or ceruloplasmin-myeloperoxidaze complexes (see Table 1). Around fragments Arg883-Arg892, His667-Trp669, and Cys699-Leu710 which are probably involved in interactions of cerruloplasmin with myeloperoxidaze [39,64,65] we found about 3, 10, and 8% populations of docked C 60 . Also, His1028-Val1037 fragment, previously recognized as important for binding various proteins to ceruloplasmin surface [66], was involved in interactions with fullerene molecules.…”

“…Fagments Arg883-Arg892 [64], His667-Trp669 [65] and loop Cys699-Leu710 [39] are probably involved in interactions of cerruloplasmin with myeloperoxidaze.…”

Peculiarities of Airway Inflammation and Lipid Peroxidation in the Development of Hyperosmotic Airway Hyperresponsiveness in Patients with Asthma

“…In halogenating or oxidative stress, the low level of CP is associated with the disturbance of its ability to form complexes with MPO and inhibit both the chlorinating and peroxide activity of the enzyme. [23,24] The low concentration of VitE found in asthma patients has an unfavorable prognostic effect on the treatment of the disease. VitE is able to regulate the biotransformation and pharmacological effect of drugs by changing the activity of xenobiotic-metabolizing enzymes, including the system of cytochrome Р450.…”