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Significant improvement of oxidase activity through the genetic incorporation of a redox-active unnatural amino acid

While nature employs various covalent and non-covalent strategies to modulate tyrosine (Y) redox potential and pK (a) in order to optimize enzyme activities, such approaches have not been systematically applied for the design of functional metalloproteins. Through the genetic incorporation of 3-meth...

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Autores principales: Yu, Yang, Zhou, Qing, Wang, Li, Liu, Xiaohong, Zhang, Wei, Hu, Meirong, Dong, Jianshu, Li, Jiasong, Lv, Xiaoxuan, Ouyang, Hanlin, Li, Han, Gao, Feng, Gong, Weimin, Lu, Yi, Wang, Jiangyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4583198/
https://www.ncbi.nlm.nih.gov/pubmed/26417427
http://dx.doi.org/10.1039/c5sc01126d
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author Yu, Yang
Zhou, Qing
Wang, Li
Liu, Xiaohong
Zhang, Wei
Hu, Meirong
Dong, Jianshu
Li, Jiasong
Lv, Xiaoxuan
Ouyang, Hanlin
Li, Han
Gao, Feng
Gong, Weimin
Lu, Yi
Wang, Jiangyun
author_facet Yu, Yang
Zhou, Qing
Wang, Li
Liu, Xiaohong
Zhang, Wei
Hu, Meirong
Dong, Jianshu
Li, Jiasong
Lv, Xiaoxuan
Ouyang, Hanlin
Li, Han
Gao, Feng
Gong, Weimin
Lu, Yi
Wang, Jiangyun
author_sort Yu, Yang
collection PubMed
description While nature employs various covalent and non-covalent strategies to modulate tyrosine (Y) redox potential and pK (a) in order to optimize enzyme activities, such approaches have not been systematically applied for the design of functional metalloproteins. Through the genetic incorporation of 3-methoxytyrosine (OMeY) into myoglobin, we replicated important features of cytochrome c oxidase (CcO) in this small soluble protein, which exhibits selective O(2) reduction activity while generating a small amount of reactive oxygen species (ROS). These results demonstrate that the electron donating ability of a tyrosine residue in the active site is important for CcO function. Moreover, we elucidated the structural basis for the genetic incorporation of OMeY into proteins by solving the X-ray structure of OMeY specific aminoacyl-tRNA synthetase complexed with OMeY.
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spelling pubmed-45831982016-07-01 Significant improvement of oxidase activity through the genetic incorporation of a redox-active unnatural amino acid Yu, Yang Zhou, Qing Wang, Li Liu, Xiaohong Zhang, Wei Hu, Meirong Dong, Jianshu Li, Jiasong Lv, Xiaoxuan Ouyang, Hanlin Li, Han Gao, Feng Gong, Weimin Lu, Yi Wang, Jiangyun Chem Sci Chemistry While nature employs various covalent and non-covalent strategies to modulate tyrosine (Y) redox potential and pK (a) in order to optimize enzyme activities, such approaches have not been systematically applied for the design of functional metalloproteins. Through the genetic incorporation of 3-methoxytyrosine (OMeY) into myoglobin, we replicated important features of cytochrome c oxidase (CcO) in this small soluble protein, which exhibits selective O(2) reduction activity while generating a small amount of reactive oxygen species (ROS). These results demonstrate that the electron donating ability of a tyrosine residue in the active site is important for CcO function. Moreover, we elucidated the structural basis for the genetic incorporation of OMeY into proteins by solving the X-ray structure of OMeY specific aminoacyl-tRNA synthetase complexed with OMeY. Royal Society of Chemistry 2015-07-01 2015-04-13 /pmc/articles/PMC4583198/ /pubmed/26417427 http://dx.doi.org/10.1039/c5sc01126d Text en This journal is © The Royal Society of Chemistry 2015 http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Chemistry
Yu, Yang
Zhou, Qing
Wang, Li
Liu, Xiaohong
Zhang, Wei
Hu, Meirong
Dong, Jianshu
Li, Jiasong
Lv, Xiaoxuan
Ouyang, Hanlin
Li, Han
Gao, Feng
Gong, Weimin
Lu, Yi
Wang, Jiangyun
Significant improvement of oxidase activity through the genetic incorporation of a redox-active unnatural amino acid
title Significant improvement of oxidase activity through the genetic incorporation of a redox-active unnatural amino acid
title_full Significant improvement of oxidase activity through the genetic incorporation of a redox-active unnatural amino acid
title_fullStr Significant improvement of oxidase activity through the genetic incorporation of a redox-active unnatural amino acid
title_full_unstemmed Significant improvement of oxidase activity through the genetic incorporation of a redox-active unnatural amino acid
title_short Significant improvement of oxidase activity through the genetic incorporation of a redox-active unnatural amino acid
title_sort significant improvement of oxidase activity through the genetic incorporation of a redox-active unnatural amino acid
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4583198/
https://www.ncbi.nlm.nih.gov/pubmed/26417427
http://dx.doi.org/10.1039/c5sc01126d
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