Solution Structure of Bovine Angiogenin by ¹H Nuclear Magnetic Resonance Spectroscopy^,

Abstract

The three-dimensional structure of bovine angiogenin has been determined using two- and three-dimensional proton NMR spectroscopy. The solution structure is very close to that recently determined by X-ray diffraction analysis. This structure appears well defined, even if five loops and one helix exhibit greater flexibility. Analysis of the active site geometry confirms the position of the Glu-118 residue which obstructs the pyrimidine binding site. There is no experimental evidence of an unobstructed conformation of angiogenin in solution. In addition, it appears that the Glu-118 and Ser-119 residues and the cell receptor binding loop may play an important role in the differences of C-terminal fragment organization and ribonucleolytic activity observed between angiogenins and ribonuclease A.

The angiogenins

“…1), as compared with the homologous region of RNase-1 and -2, became clear. Nuclear magnetic resonance (NMR) studies on the structure showed that the general structure provided by X-ray crystallography also is valid in solution, including the occluded pyrimidine-binding-site cleft [76]. In addition, the orientation of the imidazole rings of both active-site histidines is unambiguously the same as in RNase-1, supporting the idea of conserved catalytic properties between these enzymes.…”

Comparison of the dynamics of bovine and human angiogenin: a molecular dynamics study

“…It is also suggested that substrate binding will be facilitated only after some conformational changes are effected. 4 Such conformational changes have not been observed in the nmr solution structure of bovine angiogenin 8 and structures of ligand-bound angiogenin are not available as yet. Another important loop in angiogenin is the one connecting strands 4 and 5 (residues 85-92 in HAng and 86 -93 in BAng).…”

Computer modeling of human angiogenin-dinucleotide substrate interaction

“…Though angiogenin's primary biological role is that of stimulating the growth of blood vessels,2 the RNase activity nevertheless seems to be an important function of the protein 3. Structural information on angiogenin has so far been confined to only the native form and its mutants 4–8…”