Enzyme Redesign Guided by Cancer-Derived IDH1 Mutations

Mutations in an enzyme can result in a neomorphic catalytic activity in cancers. We applied cancer-associated mutations from isocitrate dehydrogenases (IDHs) to homologous residues in the active sites of homoisocitrate dehydrogenases (HIDHs) to derive enzymes that catalyze the conversion of 2-oxoadi...

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Autores principales: Reitman, Zachary J., Choi, Bryan D., Spasojevic, Ivan, Bigner, Darell D., Sampson, John H., Yan, Hai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2012
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3487689/
https://www.ncbi.nlm.nih.gov/pubmed/23001033
http://dx.doi.org/10.1038/nchembio.1065
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author Reitman, Zachary J.
Choi, Bryan D.
Spasojevic, Ivan
Bigner, Darell D.
Sampson, John H.
Yan, Hai
author_facet Reitman, Zachary J.
Choi, Bryan D.
Spasojevic, Ivan
Bigner, Darell D.
Sampson, John H.
Yan, Hai
author_sort Reitman, Zachary J.
collection PubMed
description Mutations in an enzyme can result in a neomorphic catalytic activity in cancers. We applied cancer-associated mutations from isocitrate dehydrogenases (IDHs) to homologous residues in the active sites of homoisocitrate dehydrogenases (HIDHs) to derive enzymes that catalyze the conversion of 2-oxoadipate to (R)-2-hydroxyadipate, a critical step for adipic acid production. Thus, we provide a prototypic example of how insights from cancer genome sequencing and functional studies can aid in enzyme redesign.
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spelling pubmed-34876892013-05-01 Enzyme Redesign Guided by Cancer-Derived IDH1 Mutations Reitman, Zachary J. Choi, Bryan D. Spasojevic, Ivan Bigner, Darell D. Sampson, John H. Yan, Hai Nat Chem Biol Article Mutations in an enzyme can result in a neomorphic catalytic activity in cancers. We applied cancer-associated mutations from isocitrate dehydrogenases (IDHs) to homologous residues in the active sites of homoisocitrate dehydrogenases (HIDHs) to derive enzymes that catalyze the conversion of 2-oxoadipate to (R)-2-hydroxyadipate, a critical step for adipic acid production. Thus, we provide a prototypic example of how insights from cancer genome sequencing and functional studies can aid in enzyme redesign. 2012-09-23 2012-11 /pmc/articles/PMC3487689/ /pubmed/23001033 http://dx.doi.org/10.1038/nchembio.1065 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Reitman, Zachary J.
Choi, Bryan D.
Spasojevic, Ivan
Bigner, Darell D.
Sampson, John H.
Yan, Hai
Enzyme Redesign Guided by Cancer-Derived IDH1 Mutations
title Enzyme Redesign Guided by Cancer-Derived IDH1 Mutations
title_full Enzyme Redesign Guided by Cancer-Derived IDH1 Mutations
title_fullStr Enzyme Redesign Guided by Cancer-Derived IDH1 Mutations
title_full_unstemmed Enzyme Redesign Guided by Cancer-Derived IDH1 Mutations
title_short Enzyme Redesign Guided by Cancer-Derived IDH1 Mutations
title_sort enzyme redesign guided by cancer-derived idh1 mutations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3487689/
https://www.ncbi.nlm.nih.gov/pubmed/23001033
http://dx.doi.org/10.1038/nchembio.1065
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