3RDB

Human Cyclophilin D Complexed with a Fragment

Summary for 3RDB

• Entry DOI: 10.2210/pdb3rdb/pdb
• Related: 3R49 3R4G 3R54 3R56 3R57 3R59 3RCF 3RCG 3RCI 3RCK 3RCL 3RD9 3RDA 3RDC 3RDD
• Descriptor: Peptidyl-prolyl cis-trans isomerase F, mitochondrial, O-ACETALDEHYDYL-HEXAETHYLENE GLYCOL, 3-[5-(chloromethyl)-1,2,4-oxadiazol-3-yl]aniline, ... (4 entities in total)
• Functional Keywords: beta barrel, prolyl cis/trans isomerase, mitochondria, inhibitor, isomerase-isomerase inhibitor complex, isomerase/isomerase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Mitochondrion matrix : P30405
• Total number of polymer chains: 1
• Total formula weight: 18404.40

Authors

Colliandre, L.,Ahmed-Belkacem, H.,Bessin, Y.,Pawlotsky, J.M.,Guichou, J.F. (deposition date: 2011-04-01, release date: 2012-03-21, Last modification date: 2023-09-13)

Primary citation

Ahmed-Belkacem, A.,Colliandre, L.,Ahnou, N.,Nevers, Q.,Gelin, M.,Bessin, Y.,Brillet, R.,Cala, O.,Douguet, D.,Bourguet, W.,Krimm, I.,Pawlotsky, J.M.,Guichou, J.F.
Fragment-based discovery of a new family of non-peptidic small-molecule cyclophilin inhibitors with potent antiviral activities.
Nat Commun, 7:12777-12777, 2016

PubMed Abstract: 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.

PubMed: 27652979
DOI: 10.1038/ncomms12777

Experimental method

X-RAY DIFFRACTION (1.55 Å)