1GV7

ARH-I, an angiogenin/RNase A chimera

Summary for 1GV7

• Entry DOI: 10.2210/pdb1gv7/pdb
• Related: 1A4Y 1ANG 1AWZ 1B1E 1B1I 1B1J 1H52 1H53 1HBY 2ANG
• Descriptor: ANGIOGENIN, CITRIC ACID (3 entities in total)
• Functional Keywords: hydrolase, pancreatic ribonuclease, angiogenesis, angiogenin, chimera, hybrid, homolog scanning mutagenesis
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 1
• Total formula weight: 14167.97

Authors

Holloway, D.E.,Shapiro, R.,Hares, M.C.,Leonidas, D.D.,Acharya, K.R. (deposition date: 2002-02-06, release date: 2002-08-22, Last modification date: 2024-11-06)

Primary citation

Holloway, D.E.,Shapiro, R.,Hares, M.C.,Leonidas, D.D.,Acharya, K.R.
Guest-Host Crosstalk in an Angiogenin-RNase A Chimeric Protein
Biochemistry, 41:10482-, 2002

PubMed Abstract: Angiogenin and ribonuclease A share 33% sequence identity but have distinct functions. Angiogenin is a potent inducer of angiogenesis that is only weakly ribonucleolytic, whereas ribonuclease A is a robust ribonuclease that is not angiogenic. A chimera ("ARH-I"), in which angiogenin residues 58-70 are replaced with residues 59-73 of ribonuclease A, has intermediate ribonucleolytic potency and no angiogenic activity. Here we report a crystal structure of ARH-I that reveals the molecular basis for these characteristics. The ribonuclease A-derived (guest) segment adopts a structure largely similar to that in ribonuclease A, and successfully converts this region from a cell-binding site to a purine-binding site. At the same time, its presence causes complex changes in the angiogenin-derived (host) portion that account for much of the increased ribonuclease activity of ARH-I. Guest-host interactions of this type probably occur more generally in protein chimeras, emphasizing the importance of direct structural information for understanding the functional behavior of such molecules.

PubMed: 12173935
DOI: 10.1021/BI026151R

Experimental method

X-RAY DIFFRACTION (2.1 Å)