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

Authors: Kontopidis, George; Taylor, Paul; Walkinshaw, Malcolm D.

Source: Acta Crystallographica Section D, Volume 60, Number 3, March 2004 , pp. 479-485(7)

Publisher: Blackwell Publishing

Key:

- Free Content

- New Content

- Subscribed Content

- Free Trial Content

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.

Keywords: immunophilin; cyclosporin A; cyclophilin; ligand binding; molecular recognition

Document Type: Research article

DOI: 10.1107/S0907444904000174

The full text electronic article is available for purchase. You will be able to download the full text electronic article after payment.

$50.16 plus tax Refund Policy