Acta Crystallographica Section D 2004-03-01

Enzymatic and structural characterization of non-peptide ligand-cyclophilin complexes.

George Kontopidis, Paul Taylor, Malcolm D Walkinshaw

文献索引：Acta Crystallogr. D Biol. Crystallogr. 60(Pt 3) , 479-85, (2004)

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摘要

Piperidine ligands are described that provide the first examples of non-peptidic ligand structures for the cyclophilin family of proteins. Crystal structures of two ligand complexes are compared with the unliganded protein and show ligand-induced changes in side-chain conformation and water binding. A peptidylprolyl cis-trans-isomerase assay showed the dissociation constants of the two ligands to be 320 and 25 mM. This study also provides the first published data for both enzymatic activity and three-dimensional structure for any protein-ligand complex that binds with a high-millimolar dissociation constant. The structures may be of relevance in the field of drug design, as they suggest starting points for the design of larger tighter-binding analogues.