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

Paola Estrada, Miglena Manandhar, Shi Hui Dong, Jaigeeth Deveryshetty, Vinayak Agarwal, John E. Cronan, Satish K. Nair

Research output: Contribution to journalArticlepeer-review


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 ‰-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.

Original languageEnglish (US)
Pages (from-to)668-674
Number of pages7
JournalNature chemical biology
Issue number6
StatePublished - Jun 1 2017

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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