Application of a proteolysis/mass spectrometry method for investigating the effects of inhibitors on hydroxylase structure.

Journal article

Limited proteolysis coupled to matrix-assisted laser desorption/ionization (MALDI) mass spectrometric analyses can be used to screen for compounds that alter protein structure by monitoring stabilizing/destabilizing effects with respect to the rate and nature of proteolysis. When applied to prolyl hydroxylase 2, a key enzyme involved in human oxygen sensing, the method efficiently revealed differential effects on proteolytic stability for structurally similar compounds and for different substrates.

Authors: Stubbs, C; Loenarz, C; Mecinović, J; Yeoh, K; Hindley, N

• Publication status: Published
• Journal: Journal of medicinal chemistry
• Volume: 52
• Issue: 9
• Pages: 2799-2805
• Publication date: 2009-05-01
• DOI: 10.1021/jm900285r
• EISSN: 1520-4804
• ISSN: 0022-2623
• Language: English
• Keywords: Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Protein Stability; Enzyme Inhibitors; Models, Molecular; Peptide Fragments; Catalytic Domain; Humans; Inhibitory Concentration 50; Hypoxia-Inducible Factor 1, alpha Subunit; Mixed Function Oxygenases; Animals