Molecular recognition of human eosinophil-derived neurotoxin (RNase 2) by placental ribonuclease inhibitor.
Placental ribonuclease inhibitor (RI) binds diverse mammalian RNases with dissociation constants that are in the femtomolar range. Previous studies on the complexes of RI with RNase A and angiogenin revealed that RI utilises largely distinctive interactions to achieve high affinity for these two ligands. Here we report a 2.0 angstroms resolution crystal structure of RI in complex with a third ligand, eosinophil-derived neurotoxin (EDN), and a mutational analysis based on this structure. The RI-EDN interface is more extensive than those of the other two complexes and contains a considerably larger set of interactions. Few of the contacts present in the RI-angiogenin complex are replicated; the correspondence to the RI-RNase A complex is somewhat greater, but still modest. The energetic contributions of various interface regions differ strikingly from those in the earlier complexes. These findings provide insight into the structural basis for the unusual combination of high avidity and relaxed stringency that RI displays.
Iyer
Shalini
S
Department of Biology and Biochemistry, 4 South, University of Bath, Claverton Down, Bath BA2 7AY, UK.
Holloway
Daniel E
DE
Kumar
Kapil
K
Shapiro
Robert
R
Acharya
K Ravi
KR
D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism; D047208:Eosinophil-Derived Neurotoxin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010926:Placental Hormones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D012259:Ribonuclease, Pancreatic / Q000737:chemistry / Q000235:genetics; D013552:Swine
D004791:Enzyme Inhibitors; D008024:Ligands; D010926:Placental Hormones; C022052:placental ribonuclease inhibitor; D047208:Eosinophil-Derived Neurotoxin; C046366:angiogenin; D012259:Ribonuclease, Pancreatic