The crystal structure of human angiogenin in complex with an antitumor neutralizing antibody.
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Chavali GB, Papageorgiou AC, Olson KA, Fett JW, Hu Gf, Shapiro R, Acharya KR
The crystal structure of human angiogenin in complex with an antitumor neutralizing antibody.
Structure. 2003 Jul;11(7):875-85.
- PubMed ID
- 12842050 [ View in PubMed]
- Abstract
The murine monoclonal antibody 26-2F neutralizes the angiogenic and ribonucleolytic activities of human angiogenin (ANG) and is highly effective in preventing the establishment and metastatic dissemination of human tumors in athymic mice. Here we report a 2.0 A resolution crystal structure for the complex of ANG with the Fab fragment of 26-2F that reveals the detailed interactions between ANG and the complementarity-determining regions (CDRs) of the antibody. Surprisingly, Fab binding induces a dramatic conformational change in the cell binding region of ANG at the opposite end of the molecule from the combining site; crosslinking experiments indicate that this rearrangement also occurs in solution. The ANG-Fab complex structure should be invaluable for designing maximally humanized versions of 26-2F for potential clinical use.