The STUB1 gene (STIP1 homology and U-box containing protein 1, E3 ubiquitin protein ligase) encodes CHIP, which is an E3 ubiquitin protein ligase. The role of ubiquitin ligases is to recognize the target protein to be ubiquitinated and mediate the attachment of ubiquitin. Recent evidence suggests that deletion of STUB1─a pivotal negative regulator of interferon-γ sensing─may potentially clear malignant cells. However, current studies rely primarily on genetic approaches, as pharmacological inhibitors of STUB1 are lacking. Identifying a tool compound will be a step toward validating the target in a broader therapeutic sense. Herein, screening more than a billion macrocyclic peptides resulted in STUB1 binders, which were further optimized by a structure-enabled in silico design. Here you can see how a macrocyclic peptide interacts with the molecular surface of STUB1 as determined by X-ray diffraction (PDB code: 7TB1)
#molecularart ... #immolecular ... #interferon ... #stub1 ... #peptide ... #drugdesign ... #insilico ... #xray
Structure of the STUB1-peptide complex rendered with @proteinimaging and depicted with @corelphotopaint
#molecularart ... #immolecular ... #interferon ... #stub1 ... #peptide ... #drugdesign ... #insilico ... #xray
Structure of the STUB1-peptide complex rendered with @proteinimaging and depicted with @corelphotopaint
