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.
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Authors | Gayatri B Chavali, Anastassios C Papageorgiou, Karen A Olson, James W Fett, Guo fu Hu, Robert Shapiro, K Ravi Acharya |
Journal | Structure (London, England : 1993)
(Structure)
Vol. 11
Issue 7
Pg. 875-85
(Jul 2003)
ISSN: 0969-2126 [Print] United States |
PMID | 12842050
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Complementarity Determining Regions
- Immunoglobulin Fab Fragments
- angiogenin
- Ribonuclease, Pancreatic
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Topics |
- Amino Acid Sequence
- Complementarity Determining Regions
- Epitope Mapping
- Humans
- Immunoglobulin Fab Fragments
(chemistry, immunology)
- Molecular Sequence Data
- Neoplasms
(immunology)
- Neutralization Tests
- Protein Conformation
- Ribonuclease, Pancreatic
(chemistry, immunology)
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