Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Catalytic Domain / drug effects
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Enzyme Inhibitors / metabolism
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Enzyme Inhibitors / pharmacology*
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / chemistry
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
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Inhibitory Concentration 50
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Mixed Function Oxygenases / antagonists & inhibitors
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Mixed Function Oxygenases / chemistry*
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Mixed Function Oxygenases / metabolism*
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Models, Molecular
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Peptide Fragments / metabolism
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Protein Stability / drug effects
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Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Substances
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Enzyme Inhibitors
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Hypoxia-Inducible Factor 1, alpha Subunit
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Peptide Fragments
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Mixed Function Oxygenases