Role of the surface loop on the structure and biological activity of angiogenin.
Angiogenin is a member of the ribonuclease superfamily that induces the formation of new blood vessels. It has been suggested that the surface loop of angiogenin defined by residues 59-71 plays a special role in angiogenic function (1); however, the mechanism of action is not clearly defined. To elucidate the role of the surface loop on the structure, function and stability of angiogenin, three surface loop mutants were produced in which 14 amino acids in the surface loop of RNase A were substituted for the 13 amino acids in the corresponding loop of angiogenin. The structure, stability and biological functions of the mutants were then investigated using biophysical and biological approaches. Even though the substitutions did not influence the overall structure of angiogenin, they affected the stability and angiogenic function of angiogenin, indicating that the surface loop of angiogenin plays a significant role in maintaining the stability and angiogenic function of angiogenin.
Jang
Seung Hwan
SH
Department of Bioinformatics and Life Science, and CAMDRC, Soongsil University, Seoul 156-743, Korea.
Song
Hyang Do
HD
Kang
Dong Ku
DK
Chang
Soo Ik
SI
Kim
Min Kyung
MK
Cho
Kwang Hwi
KH
Scheraga
Harold A
HA
Shin
Hang Cheol
HC
D004795:Enzyme Stability; D009154:Mutation; D011487:Protein Conformation; D012259:Ribonuclease, Pancreatic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013499:Surface Properties
C046366:angiogenin; D012259:Ribonuclease, Pancreatic