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The crystal structure of a Fab fragment to the melanoma-associated GD2 ganglioside.

Abstract
The GD2 ganglioside is a cell-surface component that appears on the surface of metastatic melanoma cells and is a marker for the progression of the disease. The ME36.1 monoclonal antibody binds to the GD2 ganglioside and has shown potential as a therapeutic antibody. ME36.1 is a possible alternative therapy to radiation, which is often ineffective in late-stage melanoma. The crystal structure of the Fab fragment of ME36.1 has been determined using molecular replacement and refined to an R factor of 20.4% at 2.8 A resolution. The model has good geometry with root-mean-square deviations of 0.008 A from ideal bond lengths and 1.7 degrees from ideal bond angles. The crystal structure of the ME36.1 Fab shows that its complementarity determining region forms a groove-shaped binding site rather than the pocket-type observed in other sugar binding Fabs. Molecular modeling has placed a four-residue sugar, representative of GD2, in the antigen binding site. The GD2 sugar moiety is stabilized by a network of hydrogen bonds that define the specificity of ME36.1 toward its antigen.
AuthorsS L Pichla, R Murali, R M Burnett
JournalJournal of structural biology (J Struct Biol) Vol. 119 Issue 1 Pg. 6-16 (Jun 1997) ISSN: 1047-8477 [Print] United States
PMID9216084 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antibodies, Monoclonal
  • Gangliosides
  • Immunoglobulin Fab Fragments
  • Immunoglobulin Variable Region
  • ganglioside, GD2
Topics
  • Antibodies, Monoclonal (chemistry, immunology)
  • Binding Sites, Antibody
  • Carbohydrate Conformation
  • Carbohydrate Sequence
  • Crystallization
  • Crystallography, X-Ray
  • Gangliosides (chemistry, immunology)
  • Hydrogen Bonding
  • Immunoglobulin Fab Fragments (chemistry, immunology)
  • Immunoglobulin Variable Region
  • Melanoma (chemistry, immunology, therapy)
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Structure
  • Protein Conformation
  • Software

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