Purification, crystallization and preliminary X-ray analysis of the Fab fragment from MNAC13, a novel antagonistic anti-tyrosine kinase A receptor monoclonal antibody

The monoclonal antibody MNAC13 is a potent antagonist that prevents the bin ding of nerve-growth factor (NGF) to its tyrosine kinase A receptor (TrkA) in a variety of systems. Structural studies of the FabMNAC13 fragment were performed to gain insights into the mechanism of action of this potentially therapeutic monoclonal antibody. The optimal conditions for crystallizatio n of FabMNAC13 were determined. Crystals appeared as prismatic bundles, dis played P2(1)2(1)2(1) space-group symmetry and diffracted to a resolution of 1.8 Angstrom. The unit-cell parameters were determined to be a = 52.73, b = 67.55, c = 111.43 Angstrom. The data set was 99.5% complete. Molecular re placement was performed, resulting in a correlation coefficient of 0.55 and an R value of 0.40. The structure refinement is now in progress.