TY - JOUR
T1 - Three-dimensional crystal structure of human eosinophil cationic protein (RNase 3) at 1.75 Å resolution
AU - Mallorquí-Fernández, Goretti
AU - Pous, Joan
AU - Peracaula, Rosa
AU - Aymamí, Joan
AU - Maeda, Takashi
AU - Tada, Hiroko
AU - Yamada, Hidenori
AU - Seno, Masaharu
AU - De Llorens, Rafael
AU - Gomis-Rüth, F. Xavier
AU - Coll, Miquel
N1 - Funding Information:
We are grateful to Professor M. James for making the coordinates of EDN available to us. This work was supported by the Ministerio de Educación y Cultura (grants PB98–1631 & 2FD97-0518) and the Generalitat de Catalunya (Centre de Referència en Biotecnologia and grant 1997SGR-275) (to M.C.) and SAF98-0086 and FEDER 2FD97-0872 and the Generalitat de Catalunya (Grup consolidat SGR97-240) (to R.L.). G.M. and J.P. are the recipients of predoctoral fellowships from Universitat de Girona and Ministerio de Educación y Cultura of Spain, respectively. H.Y. and M.S. were supported by Grant-in-Aid for Scientific Research from the Ministery of Education, Science, Sports and Culture of Japan.
PY - 2000/7/28
Y1 - 2000/7/28
N2 - Eosinophil cationic protein (ECP; RNase 3) is a human ribonuclease found only in eosinophil leukocytes that belongs to the RNase A superfamily. This enzyme is bactericidal, helminthotoxic and cytotoxic to mammalian cells and tissues. The protein has been cloned, heterologously overexpressed, purified and crystallized. Its crystal structure has been determined and refined using data up to 1.75 Å resolution. The molecule displays the α + β folding topology typical for members of the ribonuclease A superfamily. The catalytic active site residues are conserved with respect to other ribonucleases of the superfamily but some differences appear at substrate recognition subsites, which may account, in part, for the low catalytic activity. Most strikingly, 19 surface-located arginine residues confer a strong basic character to the protein. The high concentration of positive charges and the particular orientation of the side-chains of these residues may also be related to the low activity of ECP as a ribonuclease and provides an explanation for its unique cytotoxic role through cell membrane disruption. (C) 2000 Academic Press.
AB - Eosinophil cationic protein (ECP; RNase 3) is a human ribonuclease found only in eosinophil leukocytes that belongs to the RNase A superfamily. This enzyme is bactericidal, helminthotoxic and cytotoxic to mammalian cells and tissues. The protein has been cloned, heterologously overexpressed, purified and crystallized. Its crystal structure has been determined and refined using data up to 1.75 Å resolution. The molecule displays the α + β folding topology typical for members of the ribonuclease A superfamily. The catalytic active site residues are conserved with respect to other ribonucleases of the superfamily but some differences appear at substrate recognition subsites, which may account, in part, for the low catalytic activity. Most strikingly, 19 surface-located arginine residues confer a strong basic character to the protein. The high concentration of positive charges and the particular orientation of the side-chains of these residues may also be related to the low activity of ECP as a ribonuclease and provides an explanation for its unique cytotoxic role through cell membrane disruption. (C) 2000 Academic Press.
KW - Cytotoxicity
KW - Eosinophil cationic protein (ECP)
KW - RNase 3
KW - X-ray crystal structure
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U2 - 10.1006/jmbi.2000.3939
DO - 10.1006/jmbi.2000.3939
M3 - Article
C2 - 10903870
AN - SCOPUS:0034725562
VL - 300
SP - 1297
EP - 1307
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
SN - 0022-2836
IS - 5
ER -