Crystallization of the complex between cyclophilin A and cyclosporin derivatives: the use of cross-seeding.
With ammonium sulfate as the precipitant, different crystal forms of the complex between cyclosporin A (CsA) and cyclophilin A (CypA) have been crystal- lized [Zurini, Kallen, Mikol, Pflügl, Jansonius & Walkinshaw (1990). FEBS Lett. 276, 63-66]. All have large unit cells and contain a pentamer or a decamer in the asymmetric unit. Using a more water soluble CsA analog, orthorhombic crystals containing only one molecule per asymmetric unit could be grown. They diffract to significantly higher resolution (2.1 A). In this crystal form, CsA has no packing interactions with neighbouring molecules and these crystals could be used to cross-seed other CypA/CsA analog complexes. Nine different CypA/ CsA analog complexes could be crystallized using this technique, most of them yielding highly diffracting crystals, quickly solvable by Fourier difference methods.
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Preclinical Research, Sandoz AG, Basle, Switzerland.
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