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The crystal structure of human angiogenin in complex with an antitumor neutralizing antibody.

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.
AuthorsGayatri B Chavali, Anastassios C Papageorgiou, Karen A Olson, James W Fett, Guo fu Hu, Robert Shapiro, K Ravi Acharya
JournalStructure (London, England : 1993) (Structure) Vol. 11 Issue 7 Pg. 875-85 (Jul 2003) ISSN: 0969-2126 [Print] United States
PMID12842050 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Complementarity Determining Regions
  • Immunoglobulin Fab Fragments
  • angiogenin
  • Ribonuclease, Pancreatic
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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