| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2530062 | Current Opinion in Pharmacology | 2011 | 7 Pages |
The FK506 binding protein (FKBP) family of proteins provide an interesting series of drug targets since different isoforms modulate diverse cellular pathways. There are therapeutic opportunities in the fields of cancer therapy, neurodegenerative conditions and psychiatric disorders. X-ray crystallographic or NMR data are available for eight of fourteen human FKBPs covering ten of the twenty-two different FKBP domains. We have made a detailed sequence and structural comparison of human FKBP domains. These data show that the chemical scaffolds common to the immunosuppressive inhibitors FK506 and rapamycin bind to the most conserved region of the binding site. This observation opens the way to the design of isoform specific inhibitors.
Graphical abstractFigure optionsDownload full-size imageDownload high-quality image (174 K)Download as PowerPoint slideHighlights► Despite new assay developments, no new isoform-specific FKBP inhibitors have been published. ► New fluorescent probes have been designed for high-throughput binding screens. ► Sequence comparison between 22 FKBP domains shows identity from 17 to 83%. ► Structural alignment shows a partially conserved binding pocket among all 22 FKBP domains. ► FKBP38 shows the most discrimination in binding FKK06 and rapamycin.
