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

George Kontopidis, Paul Taylor, Malcolm D Walkinshaw

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)479-85
Number of pages7
JournalActa Crystallographica Section D: Biological Crystallography
Volume60
Issue numberPt 3
DOIs
Publication statusPublished - 2004

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