Cargando…
A ribose-functionalized NAD(+) with unexpected high activity and selectivity for protein poly-ADP-ribosylation
Nicotinamide adenine dinucleotide (NAD(+))-dependent ADP-ribosylation plays important roles in physiology and pathophysiology. It has been challenging to study this key type of enzymatic post-translational modification in particular for protein poly-ADP-ribosylation (PARylation). Here we explore che...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744458/ https://www.ncbi.nlm.nih.gov/pubmed/31519936 http://dx.doi.org/10.1038/s41467-019-12215-4 |
_version_ | 1783451374503067648 |
---|---|
author | Zhang, Xiao-Nan Cheng, Qinqin Chen, Jingwen Lam, Albert T. Lu, Yanran Dai, Zhefu Pei, Hua Evdokimov, Nikolai M. Louie, Stan G. Zhang, Yong |
author_facet | Zhang, Xiao-Nan Cheng, Qinqin Chen, Jingwen Lam, Albert T. Lu, Yanran Dai, Zhefu Pei, Hua Evdokimov, Nikolai M. Louie, Stan G. Zhang, Yong |
author_sort | Zhang, Xiao-Nan |
collection | PubMed |
description | Nicotinamide adenine dinucleotide (NAD(+))-dependent ADP-ribosylation plays important roles in physiology and pathophysiology. It has been challenging to study this key type of enzymatic post-translational modification in particular for protein poly-ADP-ribosylation (PARylation). Here we explore chemical and chemoenzymatic synthesis of NAD(+) analogues with ribose functionalized by terminal alkyne and azido groups. Our results demonstrate that azido substitution at 3′-OH of nicotinamide riboside enables enzymatic synthesis of an NAD(+) analogue with high efficiency and yields. Notably, the generated 3′-azido NAD(+) exhibits unexpected high activity and specificity for protein PARylation catalyzed by human poly-ADP-ribose polymerase 1 (PARP1) and PARP2. And its derived poly-ADP-ribose polymers show increased resistance to human poly(ADP-ribose) glycohydrolase-mediated degradation. These unique properties lead to enhanced labeling of protein PARylation by 3′-azido NAD(+) in the cellular contexts and facilitate direct visualization and labeling of mitochondrial protein PARylation. The 3′-azido NAD(+) provides an important tool for studying cellular PARylation. |
format | Online Article Text |
id | pubmed-6744458 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-67444582019-09-16 A ribose-functionalized NAD(+) with unexpected high activity and selectivity for protein poly-ADP-ribosylation Zhang, Xiao-Nan Cheng, Qinqin Chen, Jingwen Lam, Albert T. Lu, Yanran Dai, Zhefu Pei, Hua Evdokimov, Nikolai M. Louie, Stan G. Zhang, Yong Nat Commun Article Nicotinamide adenine dinucleotide (NAD(+))-dependent ADP-ribosylation plays important roles in physiology and pathophysiology. It has been challenging to study this key type of enzymatic post-translational modification in particular for protein poly-ADP-ribosylation (PARylation). Here we explore chemical and chemoenzymatic synthesis of NAD(+) analogues with ribose functionalized by terminal alkyne and azido groups. Our results demonstrate that azido substitution at 3′-OH of nicotinamide riboside enables enzymatic synthesis of an NAD(+) analogue with high efficiency and yields. Notably, the generated 3′-azido NAD(+) exhibits unexpected high activity and specificity for protein PARylation catalyzed by human poly-ADP-ribose polymerase 1 (PARP1) and PARP2. And its derived poly-ADP-ribose polymers show increased resistance to human poly(ADP-ribose) glycohydrolase-mediated degradation. These unique properties lead to enhanced labeling of protein PARylation by 3′-azido NAD(+) in the cellular contexts and facilitate direct visualization and labeling of mitochondrial protein PARylation. The 3′-azido NAD(+) provides an important tool for studying cellular PARylation. Nature Publishing Group UK 2019-09-13 /pmc/articles/PMC6744458/ /pubmed/31519936 http://dx.doi.org/10.1038/s41467-019-12215-4 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Zhang, Xiao-Nan Cheng, Qinqin Chen, Jingwen Lam, Albert T. Lu, Yanran Dai, Zhefu Pei, Hua Evdokimov, Nikolai M. Louie, Stan G. Zhang, Yong A ribose-functionalized NAD(+) with unexpected high activity and selectivity for protein poly-ADP-ribosylation |
title | A ribose-functionalized NAD(+) with unexpected high activity and selectivity for protein poly-ADP-ribosylation |
title_full | A ribose-functionalized NAD(+) with unexpected high activity and selectivity for protein poly-ADP-ribosylation |
title_fullStr | A ribose-functionalized NAD(+) with unexpected high activity and selectivity for protein poly-ADP-ribosylation |
title_full_unstemmed | A ribose-functionalized NAD(+) with unexpected high activity and selectivity for protein poly-ADP-ribosylation |
title_short | A ribose-functionalized NAD(+) with unexpected high activity and selectivity for protein poly-ADP-ribosylation |
title_sort | ribose-functionalized nad(+) with unexpected high activity and selectivity for protein poly-adp-ribosylation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744458/ https://www.ncbi.nlm.nih.gov/pubmed/31519936 http://dx.doi.org/10.1038/s41467-019-12215-4 |
work_keys_str_mv | AT zhangxiaonan aribosefunctionalizednadwithunexpectedhighactivityandselectivityforproteinpolyadpribosylation AT chengqinqin aribosefunctionalizednadwithunexpectedhighactivityandselectivityforproteinpolyadpribosylation AT chenjingwen aribosefunctionalizednadwithunexpectedhighactivityandselectivityforproteinpolyadpribosylation AT lamalbertt aribosefunctionalizednadwithunexpectedhighactivityandselectivityforproteinpolyadpribosylation AT luyanran aribosefunctionalizednadwithunexpectedhighactivityandselectivityforproteinpolyadpribosylation AT daizhefu aribosefunctionalizednadwithunexpectedhighactivityandselectivityforproteinpolyadpribosylation AT peihua aribosefunctionalizednadwithunexpectedhighactivityandselectivityforproteinpolyadpribosylation AT evdokimovnikolaim aribosefunctionalizednadwithunexpectedhighactivityandselectivityforproteinpolyadpribosylation AT louiestang aribosefunctionalizednadwithunexpectedhighactivityandselectivityforproteinpolyadpribosylation AT zhangyong aribosefunctionalizednadwithunexpectedhighactivityandselectivityforproteinpolyadpribosylation AT zhangxiaonan ribosefunctionalizednadwithunexpectedhighactivityandselectivityforproteinpolyadpribosylation AT chengqinqin ribosefunctionalizednadwithunexpectedhighactivityandselectivityforproteinpolyadpribosylation AT chenjingwen ribosefunctionalizednadwithunexpectedhighactivityandselectivityforproteinpolyadpribosylation AT lamalbertt ribosefunctionalizednadwithunexpectedhighactivityandselectivityforproteinpolyadpribosylation AT luyanran ribosefunctionalizednadwithunexpectedhighactivityandselectivityforproteinpolyadpribosylation AT daizhefu ribosefunctionalizednadwithunexpectedhighactivityandselectivityforproteinpolyadpribosylation AT peihua ribosefunctionalizednadwithunexpectedhighactivityandselectivityforproteinpolyadpribosylation AT evdokimovnikolaim ribosefunctionalizednadwithunexpectedhighactivityandselectivityforproteinpolyadpribosylation AT louiestang ribosefunctionalizednadwithunexpectedhighactivityandselectivityforproteinpolyadpribosylation AT zhangyong ribosefunctionalizednadwithunexpectedhighactivityandselectivityforproteinpolyadpribosylation |