Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.16.3.1 (
ceruloplasmin
)
5,074
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Myeloperoxidase (MPO) and
eosinophil peroxidase
(
EPO
) are involved in the development of halogenative stress during inflammation. We previously described a complex between MPO and
ceruloplasmin
(CP). Considering the high structural homology between MPO and
EPO
, we studied the latter's interaction with CP and checked whether
EPO
becomes inhibited in a complex with CP. Disc-electrophoresis and gel filtration showed that CP and
EPO
form a complex with the stoichiometry 1:1. Affinity chromatography of
EPO
on CP-agarose (150 mM NaCl, 10 mM Na-phosphate buffer, of pH 7.4) resulted in retention of
EPO
.
EPO
protects
ceruloplasmin
from limited proteolysis by plasmin. Only intact CP shifted the Soret band typical of
EPO
from 413 to 408 nm. The contact with CP likely causes changes in the heme pocket of
EPO
. Peroxidase activity of
EPO
with substrates such as guaiacol, orcinol, o-dianisidine, 4-chloro-1-naphtol, 3,3',5,5'-tetramethylbenzidine, and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonate) is inhibited by CP in a dose-dependent manner. Similar to the interaction with MPO, the larger a substrate molecule, the stronger the inhibitory effect of CP upon
EPO
. The limited proteolysis of CP abrogates its capacity to inhibit the peroxidase activity of
EPO
. The peptide RPYLKVFNPR (corresponding to amino acids 883-892 in CP) inhibits the peroxidase and chlorinating activity of
EPO
. Only the chlorinating activity of
EPO
is efficiently inhibited by CP, while the capacity of
EPO
to oxidize bromide and thiocyanate practically does not depend on the presence of CP.
EPO
enhances the p-phenylenediamine-oxidase activity of CP. The structural homology between the sites in the MPO and
EPO
molecules enabling them to contact CP is discussed.
...
PMID:Interaction of ceruloplasmin with eosinophil peroxidase as compared to its interplay with myeloperoxidase: Reciprocal effect on enzymatic properties. 2576 23
Ceruloplasmin, an acute-phase protein, can affect the activity of leukocytes through its various enzymatic activities and protein-protein interactions (with lactoferrin, myeloperoxidase,
eosinophil peroxidase
, serprocidins, and 5-lipoxygenase (5-LOX), among others). However, the molecular mechanisms of
ceruloplasmin
activity are not clearly understood. In this study, we tested the ability of two synthetic peptides, RPYLKVFNPR (883-892) (P1) and RRPYLKVFNPRR (882-893) (P2), corresponding to the indicated fragments of the
ceruloplasmin
sequence, to affect neutrophil activation. Leukotriene (LT) B4 is the primary eicosanoid product of polymorphonuclear leukocytes (PMNLs, neutrophils). We studied leukotriene synthesis in PMNLs upon interaction with Salmonella enterica serovar Typhimurium. Priming of neutrophils with phorbol 12-myristate 13-acetate (PMA) elicited the strong regulatory function of P2 peptide as a superoxide formation inducer and leukotriene synthesis inhibitor. Ceruloplasmin-derived P2 peptide appeared to be a strong inhibitor of 5-LOX product synthesis under conditions of oxidative stress.
...
PMID:Ceruloplasmin-derived peptide is the strongest regulator of oxidative stress and leukotriene synthesis in neutrophils. 2817 60
