Quantifying the Binding Interaction between the Hypoxia-Inducible Transcription Factor and the von Hippel-Lindau Suppressor.

ABSTRACT: The hypoxia-inducible transcription factors (HIF) play a central role in the human oxygen sensing signaling pathway. The binding of the von Hippel-Lindau tumor suppressor protein (pVHL)-ElonginC-ElonginB complex (VCB) to HIF-1α is highly selective for the trans-4-hydroxylation form of when Pro564 in the C-terminal oxygen-dependent degradation domain (ODDD) of HIF-1α. The binding of HIFα for VCB is increased by ∼1000-fold upon addition of a single hydroxyl group to either of two conserved proline-residues. Here, we address how this addition governs selective recognition and characterizes the strength of the interaction of this "switch-like" signaling event. A new set of molecular mechanics parameters for 4-hydroxyproline has been developed following the CHARMM force field philosophy. Using

SUBMITTER: Domene C 

PROVIDER: S-EPMC5283694 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature