PRELIMINARY STRUCTURES OF FAB-DTPA-IN AND FAB-DTPA-CD. "IMMUNOGLOBULINE MOLECULES USED AS TUMOUR MARKERS"

A. Karlsson¹, D. Pignol² & J.C. Fontecilla-Camps²

¹ Department of Molecular Biology, Swedish University of Agricultural Sciences, S-751 24 Uppsala, Sweden
² Laboratiore de Cristallographie et de Crystallogenese des Protéines. Institut de Biologie structurale Jean Pierre Ebel, CEA-CNRS, 41 Avenue des Martyrs, 380 27 Grenoble Cedex 1, France.

Binding of metal complexes to Fab molecules can be used as markers for tumour cells in cancer therapy. In order to obtain structural information on such metal-protein interactions, we have crystallised the complexes Fab734-DTPA-In and Fab-734-Cd. X-ray diffraction data has been collected on the crystals at the D2AM beamline at the ESRF. Data was collected to a resolution of 2.8 A for Fab734-DTPA-In in a data set consisting of 9734 unique reflections and Rsym = 7.1 %. In the case of Fab-734-Cd, data was collected to a resolution of 2.6 A in a data set consisting of 11829 unique reflections and Rsym = 8.0 %. The phases were solved by using molecular replacement with the structure of Fab734-DTPA-Yt (unpublished results, LCCP) as an initial model. Refinement of the structures is presently carried out and the current values of the crystallographic R-factors are 24,9 % (Rfree 32.9 %) and 26.5 % (Rfree 36.5 %) for Fab734-DTPA-In and Fab-734-Cd respectively.

Comparisons of the final structures should allow us to explain the different affinities observed between each metal complex and the Fab734 molecule and could give us clues of how to increase the specificity for binding of each of the metal complexes.