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Title: The pimeloyl-CoA synthetase BioW defines a new fold for adenylate-forming enzymes

Abstract

Reactions that activate carboxylates through acyl-adenylate intermediates are found throughout biology and include acyl- and aryl-CoA synthetases and tRNA synthetases. Here we describe the characterization of Aquifex aeolicus BioW, which represents a new protein fold within the superfamily of adenylating enzymes. Substrate-bound structures identified the enzyme active site and elucidated the mechanistic strategy for conjugating CoA to the seven-carbon α,ω-dicarboxylate pimelate, a biotin precursor. Proper position of reactive groups for the two half-reactions is achieved solely through movements of active site residues, as confirmed by site-directed mutational analysis. The ability of BioW to hydrolyze adenylates of noncognate substrates is reminiscent of pre-transfer proofreading observed in some tRNA synthetases, and we show that this activity can be abolished by mutation of a single residue. These studies illustrate how BioW can carry out three different biologically prevalent chemical reactions (adenylation, thioesterification, and proofreading) in the context of a new protein fold.

Authors:
; ; ; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health (NIH)
OSTI Identifier:
1373770
Resource Type:
Journal Article
Journal Name:
Nature Chemical Biology
Additional Journal Information:
Journal Volume: 13; Journal Issue: 6; Journal ID: ISSN 1552-4450
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Estrada, Paola, Manandhar, Miglena, Dong, Shi-Hui, Deveryshetty, Jaigeeth, Agarwal, Vinayak, Cronan, John E., and Nair, Satish K. The pimeloyl-CoA synthetase BioW defines a new fold for adenylate-forming enzymes. United States: N. p., 2017. Web. doi:10.1038/nchembio.2359.
Estrada, Paola, Manandhar, Miglena, Dong, Shi-Hui, Deveryshetty, Jaigeeth, Agarwal, Vinayak, Cronan, John E., & Nair, Satish K. The pimeloyl-CoA synthetase BioW defines a new fold for adenylate-forming enzymes. United States. doi:10.1038/nchembio.2359.
Estrada, Paola, Manandhar, Miglena, Dong, Shi-Hui, Deveryshetty, Jaigeeth, Agarwal, Vinayak, Cronan, John E., and Nair, Satish K. Mon . "The pimeloyl-CoA synthetase BioW defines a new fold for adenylate-forming enzymes". United States. doi:10.1038/nchembio.2359.
@article{osti_1373770,
title = {The pimeloyl-CoA synthetase BioW defines a new fold for adenylate-forming enzymes},
author = {Estrada, Paola and Manandhar, Miglena and Dong, Shi-Hui and Deveryshetty, Jaigeeth and Agarwal, Vinayak and Cronan, John E. and Nair, Satish K.},
abstractNote = {Reactions that activate carboxylates through acyl-adenylate intermediates are found throughout biology and include acyl- and aryl-CoA synthetases and tRNA synthetases. Here we describe the characterization of Aquifex aeolicus BioW, which represents a new protein fold within the superfamily of adenylating enzymes. Substrate-bound structures identified the enzyme active site and elucidated the mechanistic strategy for conjugating CoA to the seven-carbon α,ω-dicarboxylate pimelate, a biotin precursor. Proper position of reactive groups for the two half-reactions is achieved solely through movements of active site residues, as confirmed by site-directed mutational analysis. The ability of BioW to hydrolyze adenylates of noncognate substrates is reminiscent of pre-transfer proofreading observed in some tRNA synthetases, and we show that this activity can be abolished by mutation of a single residue. These studies illustrate how BioW can carry out three different biologically prevalent chemical reactions (adenylation, thioesterification, and proofreading) in the context of a new protein fold.},
doi = {10.1038/nchembio.2359},
journal = {Nature Chemical Biology},
issn = {1552-4450},
number = 6,
volume = 13,
place = {United States},
year = {2017},
month = {4}
}

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