X-ray structure of a monomeric cyclophilin A-cyclosporin A crystal complex at 2.1 A resolution.

The crystal structure of a complex between recombinant human cyclophilin A (Cyp) and cyclosporin A (CsA) has been determined from a novel orthorhombic crystal form that contains only one monomer of complex per asymmetric unit rather than five in the previously determined tetragonal structure. The structure has been refined at 2.1 A resolution to a crystallographic R-factor of 16.7%. The conformation of Cyp is practically unchanged with respect to the tetragonal form. A certain number of previously undefined side-chains have been located in the electron density and a very detailed picture of the ordered solvent structure has been obtained. The interactions between CsA and Cyp are conserved. A network of the possibly conserved, water-mediated contacts is described. The structure of CsA in the monomeric complex is similar to that of the decameric complex, but shows a few small differences in the so-called effector domain of CsA, probably due to differences in crystal environment. The fact that this monomeric crystal form can be obtained shows that the formation of pentamer or decamer complexes is not a generally observed phenomenon and is not a prerequisite for biological activity.