Format

Send to

Choose Destination
FEBS Lett. 2013 Sep 17;587(18):2996-3001. doi: 10.1016/j.febslet.2013.07.019. Epub 2013 Jul 22.

In silico investigation of PHD-3 specific HIF1-α proline 567 hydroxylation: a new player in the VHL/HIF-1α interaction pathway?

Author information

1
Dept. of Biology, University of Padova, Italy.

Abstract

Hypoxia inducible factor 1α (HIF-1α) regulates oxygen homeostasis in the cell through a sensing mechanism involving its hydroxylation and binding to the von Hippel-Lindau (VHL) tumor suppressor. This mechanism is mediated through hydroxylation of HIF-1α proline 564, although in vitro tests have previously shown an alternative hydroxylation at proline 567 by PHD-3. Here, molecular dynamics simulations were used to investigate the structural effect of this alternative hydroxylation. A specific hydrogen bond network rearrangement and improved electrostatic energy for hydroxylated P567 are compatible with an increase in HIF-1α binding affinity. Sequence analysis also confirms P567 to be vastly conserved during evolution, indicating a possible role for this alternative, PHD-3 driven, post translational modification in pVHL-HIF-1α complex formation.

KEYWORDS:

Cancer; Hypoxia inducible factor 1; Molecular dynamic; Sequence analysis; Structural bioinformatic; von Hippel–Lindau

PMID:
23886708
DOI:
10.1016/j.febslet.2013.07.019
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center