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.
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Authors | S L Pichla, R Murali, R M Burnett |
Journal | Journal of structural biology
(J Struct Biol)
Vol. 119
Issue 1
Pg. 6-16
(Jun 1997)
ISSN: 1047-8477 [Print] United States |
PMID | 9216084
(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 |
- Antibodies, Monoclonal
- Gangliosides
- Immunoglobulin Fab Fragments
- Immunoglobulin Variable Region
- ganglioside, GD2
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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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