TY - JOUR
T1 - Crystal structure of eosinophil cationic protein at 2.4 A resolution
AU - Boix, Ester
AU - Leonidas, Demetres D.
AU - Nikolovski, Zoran
AU - Nogués, M. Victòria
AU - Cuchillo, Claudi M.
AU - Acharya, K. Ravi
PY - 1999/12/21
Y1 - 1999/12/21
N2 - Eosinophil cationic protein (ECP) is located in the matrix of the eosinophil's large specific granule and has marked toxicity for a variety of helminth parasites, hemoflagellates, bacteria, single-stranded RNA virus, and mammalian cells and tissues. It belongs to the bovine pancreatic ribonuclease A (RNase A) family and exhibits ribonucleolytic activity which is about 100- fold lower than that of a related eosinophil ribonuclease, the eosinophil- derived neurotoxin (EDN). The crystal structure of human ECP, determined at 2.4 A, is similar to that of RNase A and EDN. It reveals that residues Gln- 14, His-15, Lys-38, Thr-42, and His-128 at the active site are conserved as in all other RNase A homologues. Nevertheless, evidence for considerable divergence of ECP is also implicit in the structure. Amino acid residues Arg- 7, Trp-10, Asn-39, His-64, and His-82 appear to play a key part in the Substrate specificity and low catalytic activity of ECP. The structure also shows how the cationic residues are distributed on the surface of the ECP molecule that may have implications for an understanding of the cytotoxicity of this enzyme.
AB - Eosinophil cationic protein (ECP) is located in the matrix of the eosinophil's large specific granule and has marked toxicity for a variety of helminth parasites, hemoflagellates, bacteria, single-stranded RNA virus, and mammalian cells and tissues. It belongs to the bovine pancreatic ribonuclease A (RNase A) family and exhibits ribonucleolytic activity which is about 100- fold lower than that of a related eosinophil ribonuclease, the eosinophil- derived neurotoxin (EDN). The crystal structure of human ECP, determined at 2.4 A, is similar to that of RNase A and EDN. It reveals that residues Gln- 14, His-15, Lys-38, Thr-42, and His-128 at the active site are conserved as in all other RNase A homologues. Nevertheless, evidence for considerable divergence of ECP is also implicit in the structure. Amino acid residues Arg- 7, Trp-10, Asn-39, His-64, and His-82 appear to play a key part in the Substrate specificity and low catalytic activity of ECP. The structure also shows how the cationic residues are distributed on the surface of the ECP molecule that may have implications for an understanding of the cytotoxicity of this enzyme.
UR - http://www.scopus.com/inward/record.url?scp=0033592925&partnerID=8YFLogxK
U2 - 10.1021/bi9919145
DO - 10.1021/bi9919145
M3 - Article
C2 - 10606511
AN - SCOPUS:0033592925
SN - 0006-2960
VL - 38
SP - 16794
EP - 16801
JO - Biochemistry
JF - Biochemistry
IS - 51
ER -