Atomic resolution (0.98 A) structure of eosinophil-derived neurotoxin.
Human eosinophil-derived neurotoxin (EDN) is a small, basic protein that belongs to the ribonuclease A superfamily. EDN displays antiviral activity and causes the neurotoxic Gordon phenomenon when injected into rabbits. Although EDN and ribonuclease A have appreciable structural similarity and a conserved catalytic triad, their peripheral substrate-binding sites are not conserved. The crystal structure of recombinant EDN (rEDN) has been determined at 0.98 A resolution from data collected at a low temperature (100 K). We have refined the crystallographic model of the structure using anisotropic displacement parameters to a conventional R-factor of 0.116. This represents the highest resolution structure of rEDN determined to date and is only the second ribonuclease structure to be determined at a resolution greater than 1.0 A. The structure provides a detailed picture of the conformational freedom at the various subsites of rEDN, and the water structure accounts for more than 50% of the total solvent content of the unit cell. This information will be crucial for the design of tight-binding inhibitors to restrain the ribonucleolytic activity of rEDN.
Swaminathan
G Jawahar
GJ
Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, U.K.
Holloway
Daniel E
DE
Veluraja
Kasinadar
K
Acharya
K Ravi
KR
D001665:Binding Sites; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D047208:Eosinophil-Derived Neurotoxin; D008958:Models, Molecular; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry; D012260:Ribonucleases / Q000737:chemistry*
D011994:Recombinant Proteins; D047208:Eosinophil-Derived Neurotoxin; D012260:Ribonucleases