Crystal structure of bovine angiogenin at 1.5-A resolution.
The capacity of angiogenin (Ang) to induce blood vessel growth is critically dependent on its ribonucleolytic activity. Crystallography and mutagenesis of human Ang have previously shown that its pyrimidine binding site is obstructed by Gln-117, implying that a conformational change is a key part of the mechanism of Ang action. The 1.5-A-resolution crystal structure of bovine Ang, in which glutamic acid is substituted for Gln-117, now confirms that a blocked active site is characteristic of these proteins. Indeed, the inactive conformation of bovine Ang is stabilized by a more extensive set of interactions than is that of human Ang. The three-dimensional structure of the putative receptor binding site is also well conserved in the two proteins. The Arg-Gly-Asp segment of this site in bovine Ang, which is replaced by Arg-Glu-Asn in human Ang, does not have a conformation typical of an integrin recognition site.
Acharya
K R
KR
School of Biology and Biochemistry, University of Bath, United Kingdom.
Shapiro
R
R
Riordan
J F
JF
Vallee
B L
BL
D000595:Amino Acid Sequence; D043925:Angiogenesis Inducing Agents / Q000737:chemistry; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D018360:Crystallography, X-Ray; D005260:Female; D018698:Glutamic Acid; D005973:Glutamine; D006801:Humans; D006860:Hydrogen Bonding; D008892:Milk / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000302:isolation & purification; D012259:Ribonuclease, Pancreatic; D017386:Sequence Homology, Amino Acid
D043925:Angiogenesis Inducing Agents; D011506:Proteins; D005973:Glutamine; D018698:Glutamic Acid; C046366:angiogenin; D012259:Ribonuclease, Pancreatic