Crystal engineering yields crystals of cyclophilin D diffracting to 1.7 A resolution.
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Schlatter D, Thoma R, Kung E, Stihle M, Muller F, Borroni E, Cesura A, Hennig M
Crystal engineering yields crystals of cyclophilin D diffracting to 1.7 A resolution.
Acta Crystallogr D Biol Crystallogr. 2005 May;61(Pt 5):513-9. Epub 2005 Apr 20.
- PubMed ID
- 15858260 [ View in PubMed]
- Abstract
In the pharmaceutical industry, knowledge of the three-dimensional structure of a specific target facilitates the drug-discovery process. Despite possessing favoured analytical properties such as high purity and monodispersion in light scattering, some proteins are not capable of forming crystals suitable for X-ray analysis. Cyclophilin D, an isoform of cyclophilin that is expressed in the mitochondria, was selected as a drug target for the treatment of cardiac disorders. As the wild-type enzyme defied all attempts at crystallization, protein engineering on the enzyme surface was performed. The K133I mutant gave crystals that diffracted to 1.7 A resolution using in-house X-ray facilities and were suitable for soaking experiments. The crystals were very robust and diffraction was maintained after soaking in 25% DMSO solution: excellent conditions for the rapid analysis of complex structures including crystallographic fragment screening.