TY - JOUR

T1 - Ceruloplasmin and myeloperoxidase in complex affect the enzymatic properties of each other

AU - Sokolov, Alexej

AU - Ageeva, Kira

AU - Pulina, Maria

AU - Cherkalina, Olga

AU - Samygina, Valeria

AU - Vlasova, Irina I.

AU - Panasenko, Oleg

AU - Zakharova, Elena

AU - Vasilyev, Vadim

N1 - Funding Information: This study was supported by RFBR grants 06-04-48602, 08-04-00532 and the program of Basic Research of the Russian Academy of Sciences Presidium ‘Basic sciences for Medicine’. The authors are grateful to Professor V. N. Kokryakov and Professor M. M. Shavlovski (Institute of Experimental Medicine, St. Petersburg) for granted materials, valuable advice and constructive discussions.

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

KW - Activating enzyme

KW - Ceruloplasmin

KW - Inhibitory enzyme

KW - Limited proteolysis

KW - Myeloperoxidase

KW - Protein-protein interaction

UR - http://www.scopus.com/inward/record.url?scp=57649201397&partnerID=8YFLogxK

U2 - 10.1080/10715760802566574

DO - 10.1080/10715760802566574

M3 - Article

C2 - 19031316

AN - SCOPUS:57649201397

VL - 42

SP - 989

EP - 998

JO - Free Radical Research

JF - Free Radical Research

SN - 1071-5762

IS - 11-12

ER -