title: High-resolution crystal structures of two crystal forms of human cyclophilin D in complex with PEG 400 molecules.
abstract: Cyclophilin D (CypD) is a key mitochondrial target for amyloid-β-induced mitochondrial and synaptic dysfunction and is considered a potential drug target for Alzheimer's disease. The high-resolution crystal structures of primitive orthorhombic (CypD-o) and primitive tetragonal (CypD-t) forms have been determined to 1.45 and 0.85 Å resolution, respectively, and are nearly identical structurally. Although an isomorphous structure of CypD-t has previously been reported, the structure reported here was determined at atomic resolution, while CypD-o represents a new crystal form for this protein. In addition, each crystal form contains a PEG 400 molecule bound to the same region along with a second PEG 400 site in CypD-t which occupies the cyclosporine A inhibitor binding site of CypD. Highly precise structural information for CypD should be extremely useful for discerning the detailed interaction of small molecules, particularly drugs and/or inhibitors, bound to CypD. The 0.85 Å resolution structure of CypD-t is the highest to date for any CypD structure.
authors.affiliation: Department of Pharmacology and Toxicology and Higuchi Bioscience Center, University of Kansas, Lawrence, KS 66047, USA.
authors.forename: Koteswara Rao
authors.initials: KR
authors.lastname: Valasani
authors.affiliation: Department of Pharmacology and Toxicology and Higuchi Bioscience Center, University of Kansas, Lawrence, KS 66047, USA.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Carlson
authors.affiliation: IMCA-CAT, Hauptman-Woodward Medical Research Institute, 9700 South Cass Avenue, Building 435A, Argonne, IL 60439, USA.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Battaile
authors.affiliation: Department of Biological Sciences, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bisson
authors.affiliation: Department of Biological Sciences, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York, USA.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Wang
authors.affiliation: Protein Structure Laboratory, Del Shankel Structural Biology Center, University of Kansas, Lawrence, KS 66047, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Lovell
authors.affiliation: Department of Pharmacology and Toxicology and Higuchi Bioscience Center, University of Kansas, Lawrence, KS 66047, USA.
authors.forename: Shirley
authors.initials: S
authors.lastname: ShiDu Yan
mesh_terms: D018360:Crystallography, X-Ray; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D011092:Polyethylene Glycols / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D000081406:Peptidyl-Prolyl Isomerase F; D011092:Polyethylene Glycols; D021983:Cyclophilins
keywords: cyclophilin D