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High‐resolution crystal structures of two crystal forms of human cyclophilin D in complex with PEG 400 molecules
Author(s) -
Valasani Koteswara Rao,
Carlson Emily A.,
Battaile Kevin P.,
Bisson Andrea,
Wang Chunyu,
Lovell Scott,
Yan Shirley ShiDu
Publication year - 2014
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 37
ISSN - 2053-230X
DOI - 10.1107/s2053230x14009480
Subject(s) - cyclophilin , chemistry , crystal structure , orthorhombic crystal system , molecule , resolution (logic) , crystallography , stereochemistry , biophysics , biochemistry , biology , organic chemistry , artificial intelligence , computer science , gene
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.