Crystal structure of eosinophil cationic protein at 2.4 A resolution.
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.
Boix
E
E
Department of Biology and Biochemistry, University of Bath, UK.
Leonidas
D D
DD
Nikolovski
Z
Z
Nogués
M V
MV
Cuchillo
C M
CM
Acharya
K R
KR
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000737:chemistry; D001665:Binding Sites / Q000235:genetics; D001798:Blood Proteins / Q000737:chemistry* / Q000235:genetics; D002384:Catalysis; D018360:Crystallography, X-Ray / Q000379:methods; D004722:Endoribonucleases / Q000737:chemistry; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000201:enzymology*; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011506:Proteins / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry; D012259:Ribonuclease, Pancreatic / Q000737:chemistry; D012260:Ribonucleases / Q000737:chemistry* / Q000235:genetics; D013329:Structure-Activity Relationship; D013379:Substrate Specificity / Q000235:genetics
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D011506:Proteins; D011994:Recombinant Proteins; D004722:Endoribonucleases; D012260:Ribonucleases; C031956:2-5A-dependent ribonuclease; C046366:angiogenin; D012259:Ribonuclease, Pancreatic