4J5D: Human Cyclophilin D Complexed With An Inhibitor

Cyclophilins are peptidyl-prolyl cis/trans isomerases (PPIase) that catalyse the interconversion of the peptide bond at proline residues. Several cyclophilins play a pivotal role in the life cycle of a number of viruses. The existing cyclophilin inhibitors, all derived from cyclosporine A or sanglifehrin A, have disadvantages, including their size, potential for side effects unrelated to cyclophilin inhibition and drug-drug interactions, unclear antiviral spectrum and manufacturing issues. Here we use a fragment-based drug discovery approach using nucleic magnetic resonance, X-ray crystallography and structure-based compound optimization to generate a new family of non-peptidic, small-molecule cyclophilin inhibitors with potent in vitro PPIase inhibitory activity and antiviral activity against hepatitis C virus, human immunodeficiency virus and coronaviruses. This family of compounds has the potential for broad-spectrum, high-barrier-to-resistance treatment of viral infections.
PDB ID: 4J5DDownload
MMDB ID: 117630
PDB Deposition Date: 2013/2/8
Updated in MMDB: 2016/10
Experimental Method:
x-ray diffraction
Resolution: 1.32  Å
Source Organism:
Similar Structures:
Biological Unit for 4J5D: monomeric; determined by author and by software (PISA)
Molecular Components in 4J5D
Label Count Molecule
Protein (1 molecule)
Peptidyl-prolyl Cis-trans Isomerase F, Mitochondrial(Gene symbol: PPIF)
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB