Faculty Opinions recommendation of Structure of an HIF-1alpha -pVHL complex: hydroxyproline recognition in signaling.

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Regulation of the Chemokine Receptor CXCR4 by Hypoxia (2003, background): “pVHL acts as the recognition component of a ubiquitin E3 ligase complex, which binds HIF-1 , and loss of pVHL function results in constitutive activation of the hypoxic response (35, 55).”
Hypoxia-Inducible Factor-1 (HIF-1) (2006, unknown): “X-ray crystallographic studies of the pVHL/HIF-1 complex have revealed that pVHL has a surface pocket into which the hydroxyproline fits accurately, and the overall binding configuration is highly specific (Hon et al., 2002; Min et al., 2002).”
Lessons in PROTAC design from selective degradation with a promiscuous warhead (2017, background): “VHL has a well-characterized substrate whose molecular recognition is exquisitely specific: there is a 1,000-fold increase in binding affinity upon hydroxylation of a single proline residue of the VHL protein’s endogenous substrate HIF1a (Hon et al., 2002).”