Abstract
We have utilized a high-diversity phage display library to engineer antibody fragments (Fabs) that can modulate the activity of the enzyme isocitrate dehydrogenase 1 (IDH1). We show that a conformation-specific Fab can reactivate an IDH1 mutant associated with brain tumors. The results show that this strategy is a first step towards developing "activator drugs" for a large number of genetic disorders where mutations have disrupted protein function.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibodies, Monoclonal / pharmacology*
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Catalysis / drug effects
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Cell Surface Display Techniques
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Enzyme Activation / drug effects
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Enzyme Inhibitors / pharmacology*
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Humans
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Isocitrate Dehydrogenase / antagonists & inhibitors*
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Isocitrate Dehydrogenase / chemistry
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Isocitrate Dehydrogenase / genetics*
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Isocitrate Dehydrogenase / metabolism
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Kinetics
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Mutation*
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Peptide Library
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Thermodynamics
Substances
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Antibodies, Monoclonal
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Enzyme Inhibitors
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Peptide Library
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Isocitrate Dehydrogenase