2biu
From Proteopedia
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==Overview== | ==Overview== | ||
| - | In the pharmaceutical industry, knowledge of the three-dimensional | + | 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. |
==Disease== | ==Disease== | ||
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[[Category: mitochondrial protein]] | [[Category: mitochondrial protein]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:38:16 2008'' |
Revision as of 14:38, 21 February 2008
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CRYSTAL STRUCTURE OF HUMAN CYCLOPHILIN D AT 1.7 A RESOLUTION, DMSO COMPLEX
Contents |
Overview
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.
Disease
Known disease associated with this structure: Hypertension, salt-sensitive essential, susceptibility to OMIM:[605325]
About this Structure
2BIU is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Peptidylprolyl isomerase, with EC number 5.2.1.8 Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Crystal engineering yields crystals of cyclophilin D diffracting to 1.7 A resolution., Schlatter D, Thoma R, Kung E, Stihle M, Muller F, Borroni E, Cesura A, Hennig M, Acta Crystallogr D Biol Crystallogr. 2005 May;61(Pt 5):513-9. Epub 2005, Apr 20. PMID:15858260
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