Structural and mechanistic studies on prolyl hydroxylases

Thesis

Oxygen dependent prolyl-4-hydroxylation of the alpha-subunit of the hypoxia inducible transcription factor (HIF-alpha) plays an essential role in the hypoxic response. Hydroxylation of proline residues in the N- or C-terminal oxygen dependent degradation domains (NODD or CODD) increases the affinity of HIF-alpha to the von Hippel-Lindau protein (pVHL) by approx. 1000 fold so signalling for HIF-alpha degradation. With limiting oxygen, HIF-alpha hydroxylation slows, it dimerises with HIF-bet...

Expand abstract

Authors: Chowdhury, R

• Publication date: 2008
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: Oxford University, UK
• Language: English
• Keywords: nitric oxide; double-stranded-beta helix; 2-oxoglutarate; prolyl hydroxylase; hypoxia inducible factor; transcription; crystallography
• Subjects: Chemical crystallography; Molecular biophysics (biochemistry); Chemical biology; Cardiovascular disease; Protein folding; Protein chemistry